Systems, methods, and devices for the delivery of therapeutic or diagnostic agents - Patents.com

Abstract

The fluid injection system includes at least one fluid reservoir having a first fluid reservoir configured to inject a radiopharmaceutical and a radiation filter in fluid communication with the at least one fluid reservoir. The radiation filter is configured to retain radioactive particles from the radiopharmaceutical that pass through the radiation filter. The system further includes at least one sensor configured to detect radioactivity in at least one of the first fluid reservoir, the radiation filter, and the fluid path element in fluid communication with the radiation filter, and a controller in operative communication with the at least one sensor. The controller is programmed or configured to receive radioactivity measurements from the at least one sensor and determine based on the radioactivity measurements that an amount of radioactive particles in at least one of the first fluid reservoir, the radiation filter, and the fluid path set meets a predetermined threshold.

Description

[Technical field]

[0001] Cross-reference to related art This application claims priority to U.S. Provisional Application No. 63 / 312,145, filed February 21, 2022, U.S. Provisional Application No. 63 / 312,151, filed February 21, 2022, U.S. Provisional Application No. 63 / 312,152, filed February 21, 2022, and U.S. Provisional Application No. 63 / 312,148, filed February 21, 2022, the disclosures of which are incorporated by reference in their entireties herein. [Background technology]

[0002] The present disclosure relates to systems and methods for packaging, delivery, storage, administration and / or disposal of radiopharmaceuticals (e.g., radioactive drugs used in therapy or imaging). The present disclosure further relates to systems and methods for packaging, delivery, storage, administration and / or disposal of therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source. In another embodiment, the present disclosure relates to systems, devices and methods for delivery and filtration of radiopharmaceuticals in medical injection procedures.

[0003] Radiopharmaceuticals can be utilized for targeted radionuclide therapy (TRT) or for diagnostic imaging. Radiopharmaceuticals generally include a radioisotope (e.g., Ac-255, Lu-177, etc.), a targeting moiety or biovector (e.g., antibody, peptide, antigen, small molecule, etc.), and optionally a chelator (e.g., DOTA, NOTA, DTPA, etc.) interconnected into a single structure. In some cases, if the radioisotope is one that the human body naturally takes up into tissues or organs, the TRT can be just the radioisotope without the biovector or chelator. The radiopharmaceutical is configured to interact with a target protein on a cell, such as a cancer cell. The radiopharmaceutical can be mixed in liquid or fluid form. In some examples or embodiments, the radiopharmaceutical can be a solid particulate entrained in a fluid (e.g., a slurry suitable for injection into a patient). Administration is generally by intravenous administration into the systemic circulation.

[0004] Examples of TRT can include targeted alpha therapy (TAT) or targeted beta therapy (TBT). Such therapies can be administered as monotherapy or in combination, for example, by simultaneous or sequential administration. Radiotherapeutic agents for TAT emit primarily alpha radiation. The remainder of the emitted radiation from radiotherapeutic agents for TAT can include gamma radiation and / or beta radiation. Radiotherapeutic agents for TBT emit primarily beta radiation. The remainder of the emitted radiation for radiotherapeutic agents for TBT can include gamma radiation and / or alpha radiation. Examples of targeted alpha therapies include, but are not limited to, thorium (Th-227), actinium (Ac-225), and lead (Pb-212) based therapies. Examples of targeted beta therapies include lutetium (Lu-177), copper (Cu-67), or iodine (I-131) based therapies. Other examples of radiotherapeutic agents include alpha-radiotherapy agents that utilize radium (Ra) (e.g., the Ra-223 isotope, such as XOFIGO treatment offered by Bayer Health Care). Methods for the preparation, prepared solutions, and use of XOFIGO are described in U.S. Patent No. 5,399,633, the disclosure of which is incorporated herein by reference in its entirety.

[0005] Radiopharmaceuticals used in TRT can pose significant production, storage, delivery, administration, handling, and disposal challenges. Because the therapeutics are radioactive, they can cause radiation exposure to human health. Furthermore, given the decay properties of radiopharmaceuticals, the longer it takes to manufacture, process, and deliver the radiopharmaceutical to a patient, the less radioactivity will be present in the dose. There is a significant amount of regulation that must be followed to keep radioactive materials safely stored and available, and the regulations can affect how the medications can be stored and transported, as well as who may use or administer the radiopharmaceuticals. For example, such regulations can require care providers to undergo hundreds of hours of training to be able to administer any TRT.

[0006] Figure 1 shows a traditional supply chain for TRT. Initially, radiopharmaceuticals are manufactured in bulk at a manufacturing facility and loaded into bulk containers. A load of such containers is delivered to a nuclear pharmacy where a nuclear pharmacist draws a dose, for example, into a syringe based on the prescribed activity for a particular patient. The dose prepared for that patient is checked in a dose calibrator at the nuclear pharmacy to verify the prescribed administration and assay. The dose is calibrated at the time of injection to ensure that the dose has the required activity at the time of injection. The verified dose is then shipped to the treatment site where it is verified again in a dose calibrator. At the treatment site, the dose must typically be used within a certain number of hours of drawing the dose before the half-life of the radioactive material makes the dose no longer suitable for patient use. After administration, the used syringe is checked again in a dose calibrator to verify that the correct prescribed dose was administered to the patient.

[0007] As shown in Figure 2, the method for diagnosing, referring, and treating a patient involves multiple methods and many different medical professionals. After a patient P is diagnosed by a physician D, the physician D prescribes a dose of radiopharmaceutical based on a dosage regimen. The dose is filled by a nuclear pharmacist NP at a nuclear pharmacy to verify the dose, administer the dose, and verify that the correct dose was delivered to the patient before being delivered to an authorized user AU.

[0008] Conventional methods for the delivery and administration of TRT and other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source significantly limit their applicability and use. After considering shipping, handling, and patient schedules, the treatment site has only a limited amount of time to administer a dose to a particular patient. Challenges imposed by the variability of shipping, handling, and patient schedules can affect the effectiveness of TRT or other therapeutic or diagnostic agents, such as underdosing when delivering a pharmaceutical to a patient. Due to these challenges associated with conventional systems and methods for the delivery and administration of TRT and other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source, there is a need in the art for improved systems and methods for the delivery, handling, administration, and disposal of such therapies.

[0009] In addition, radiotherapy and radiology are rapidly expanding fields of medicine that utilize radiopharmaceuticals for both treatment and imaging procedures. Delivering radiopharmaceuticals presents several challenges. In some circumstances, the radiation emitted by the radiopharmaceutical may be dangerous to medical personnel administering the drug to a patient. In some circumstances, there may be daughter isotopes or daughter products present in the radiopharmaceutical that may be beneficial to remove or reduce prior to delivery to a patient. One example of this is strontium breakthrough in a rubidium generator, as described in U.S. Patent No. 5,399,992, the disclosure of which is incorporated herein by reference in its entirety.

[0010] Additionally, various forms of retention of the radiopharmaceutical in the patient can result in suboptimal treatment and / or adverse effects. Retention can include a condition in which the radiopharmaceutical is properly injected into the patient at the vascular, typically intravenous, administration site, but due to various characteristics of fluid flow and patient physiology, the radiopharmaceutical does not progress through the bloodstream as intended. This can result in the accumulation of radioactive particles near the administration site or elsewhere within the patient's venous structure. This may be referred to as stasis, slow clearance, or delayed clearance. Common causes include low blood flow within the blood vessel or adhesion of the radiopharmaceutical to the blood vessel wall. Extravasation is another type of retention, a condition in which the radiopharmaceutical is unintentionally injected into tissues outside the target vasculature surrounding the injection site, which can be dangerous to the patient as well.

[0011] Due to the above technical concerns and regulatory and training requirements, administration of radiopharmaceuticals has traditionally been performed only by highly specialized medical personnel, making such procedures less accessible than may be desired. Radiotherapy is heavily regulated due to its inherent challenges, and the regulations surrounding the procedure are often complex. For example, doses with an inaccuracy of 10% or more must be reported to the appropriate regulatory authorities in some jurisdictions. Due to these challenges associated with conventional systems and methods for the delivery and administration of radiopharmaceuticals and other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source, there is a need in the art for improved systems and methods for the delivery, handling, administration, and disposal of such therapies. [Prior art documents] [Patent documents]

[0012] [Patent Document 1] U.S. Patent No. 6,635,234 [Patent Document 2] U.S. Pat. No. 8,071,959 Summary of the Invention

[0013] Given the disadvantages of conventional systems and methods for the delivery, handling, administration, and disposal of TRT and other therapeutic or diagnostic agents, a better supply chain process is needed so that treatment sites can have TRT available and ready to use for longer periods of time. Additionally, improved systems and methods are needed to ensure that stored products are no longer patient specific. Instead, to be more flexible in how stored products can be utilized at treatment sites so that effective amounts of radiopharmaceuticals can be delivered to patients, treatment sites can be equipped with equipment to help administer treatment to any patient that may be present at the site on any particular day. Such patient-specific administration is accomplished without the need for dose calibrators at the treatment site, thereby reducing or eliminating the need for manual measurement and handling within a designated hot lab. Doses, volumes, and concentrations can be accurately measured at the manufacturing or filling site where it is much more efficient to use dosing and filling equipment such as multiple dose calibrators with error detection and correction, automated processing of samples, automated recording of data, and accurate weighing or volume measurement. More accurate equipment and reduction or elimination of the possibility of human error increases reliability throughout the supply chain. [Means for solving the problem]

[0014] In some embodiments or aspects of the present disclosure, a storage device configured to connect to a delivery system for delivering a therapeutic or diagnostic agent is provided. The storage device may include a housing having a chamber defined therein and a container disposed within the chamber. The container may have a distal end opposite a proximal end with an interior defined therebetween and configured to receive a therapeutic or diagnostic agent. The proximal end of the container may have an access port for accessing the interior. The storage device may further have a door associated with the housing, the door being movable relative to the housing between a closed position and an open position. In the closed position, the door may cover an opening in the housing to enclose the chamber of the housing. In the open position, the door may expose an opening in the housing for accessing the access port of the container. The storage device may further have a holder in the chamber of the housing that contacts the container to secure the container relative to the housing such that the access port of the container is disposed in the opening of the housing. The door may be movable between a closed position and an open position in response to actuation by an access mechanism of the delivery system.

[0015] In some embodiments or aspects of the disclosure, the holder may include a contact element for contacting the distal end of the container and a plurality of tabs connected to the contact element and configured to engage an inner surface of the housing to secure the distal end of the container relative to the housing. The storage device may further include a plurality of ribs within the chamber of the housing surrounding the opening. The plurality of ribs may be configured to secure the proximal end of the container relative to the housing.

[0016] In some embodiments or aspects of the disclosure, the storage device may further include a lock for locking the door in one of an open and closed position. A door cover may be connected to the housing, the door cover enclosing the door within the door chamber. The door cover may include a door access opening with a seal and a container access opening via a spike or the like, located opposite the opening of the housing. The seal may be penetrable by an access mechanism of the delivery system.

[0017] In some embodiments or aspects of the present disclosure, the storage device may further include a label or tag or data carrier on the housing that includes machine-readable verifiable data including at least one of product information, production information, prescription information, and shipping condition information. The opening in the housing may be configured to receive a spike that extends into the access port to access the therapeutic or diagnostic agent when the door is in the open position. In some embodiments or aspects, the therapeutic or diagnostic agent may be a radiopharmaceutical and the housing includes a shield configured to prevent radiation from the radiopharmaceutical from emitting from the housing.

[0018] In some embodiments or aspects of the present disclosure, an assembly is provided that is configured to connect to a delivery system for delivering a therapeutic or diagnostic agent. The assembly may include a storage device that contains the therapeutic or diagnostic agent and a fluidic cassette that is fluidly connectable to the storage device to access the therapeutic or diagnostic agent. The storage device may include a housing having a chamber defined therein and a container disposed within the chamber. The container may have an interior configured to receive the therapeutic or diagnostic agent and an access port for accessing the interior. The storage device may further include a door associated with the housing, the door being movable relative to the housing between a closed position and an open position. In the closed position, the door may cover an opening in the housing to enclose the chamber of the housing. In the open position, the door may expose an opening in the housing to access the access port of the container. The fluidic cassette may include a spike, a metering device, and a fluidic pathway set that fluidly connects the spike to the metering device. The fluidic cassette may further include an enclosure that encloses the spike, the metering device, and the fluidic pathway set. The storage device and fluid cassette may be configured to connect to a delivery system such that a door of the storage device is accessible by an access mechanism of the delivery system, and such that a spike and metering device of the fluid cassette is accessible by a delivery mechanism of the delivery system.

[0019] In some embodiments or aspects of the disclosure, the spike of the fluidic cassette may be insertable into the access port of the container when the door is moved to an open position to fluidly connect the metering device to the container via the fluidic pathway set. The fluidic pathway set may include one or more valves operable by a delivery mechanism of the delivery system to regulate the flow of fluid through the fluidic pathway elements. The fluidic cassette may be connectable to a saline source.

[0020] In some embodiments or aspects of the present disclosure, the storage device may include a guiding mechanism configured to position the storage device in a desired orientation relative to the fluidic cassette. The guiding mechanism may include one or more geometric features on the storage device. The one or more geometric features may be configured to mate with corresponding one or more geometric features on the fluidic cassette. The one or more geometric features may prevent mating between incompatible system components.

[0021] In some embodiments or aspects of the disclosure, the outlet of the metering device of the fluid cassette may be configured to connect to an infusion set to deliver a dose of the therapeutic or diagnostic agent from the container to the infusion set. The storage device may further include a label or tag on the housing that includes machine-readable verifiable data including at least one of product information, production information, prescription information, and shipping condition information. The therapeutic or diagnostic agent may be a radiopharmaceutical, and the housing includes a shield configured to prevent significant amounts of radiation from the radiopharmaceutical from emitting from the housing.

[0022] In some embodiments or aspects of the disclosure, a delivery system for delivering a therapeutic or diagnostic agent is provided. The delivery system may include an injector having a delivery mechanism and an access mechanism, and a fluid delivery assembly removably connectable to the injector. The fluid delivery assembly may include a storage device housing the therapeutic or diagnostic agent, and a fluidic cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent. The storage device may include a housing having a chamber defined therein, and a container disposed within the chamber. The container may have an interior configured to receive the therapeutic or diagnostic agent, and an access port for accessing the interior. The storage device may further include a door associated with the housing, the door being movable relative to the housing via the access mechanism of the injector between a closed position and an open position. In the closed position, the door may cover an opening in the housing to enclose the chamber of the housing. In the open position, the door may expose an opening in the housing for accessing the access port of the container. The fluidic cassette may include a spike, a metering device, and a fluidic pathway set fluidly connecting the spike to the metering device. The fluidic cassette may further include an enclosure enclosing the spike, the metering device, and the fluidic pathway set. The spike and the metering device of the fluidic cassette may be accessible by a delivery mechanism of the injector to fluidly connect the interior of the container with the metering device via the fluidic pathway set.

[0023] In some embodiments or aspects of the disclosure, the delivery system further includes an injector controller configured to determine a dose of therapeutic or diagnostic agent to be drawn from the container to the metering device based on the machine-readable authentication data on the storage device. The injector controller may be further configured to determine a dose of therapeutic or diagnostic agent to be drawn from the container to the metering device based on at least one patient parameter. The injector controller may be connected to a hospital network system, a hospital enterprise system, or other medical network. The injector controller may include multiple dosing algorithms for different predefined therapeutic or diagnostic procedures.

[0024] In some embodiments or aspects of the disclosure, the fluid path set may include one or more valves operable by the delivery mechanism of the delivery system to regulate the flow of fluid through the fluid path elements. The fluid cassette may be connectable to a saline or other flushing fluid source. The outlet of the metering device of the fluid cassette may be configured to connect to an infusion set to deliver a dose of a therapeutic or diagnostic agent from a container to the infusion set. The storage device may be configured to be removably or non-removably connectable to the fluid cassette.

[0025] In some embodiments or aspects of the disclosure, an inventory device is provided for managing the storage and disposal of used therapeutic or diagnostic agents. The inventory device may include a cart having a storage compartment accessible via a lockable door. The storage compartment may be configured to store one or more waste containers. Each waste container may include a storage device comprising a housing having a chamber defined therein and a container disposed within the chamber of the housing. The container may be configured to store a radiopharmaceutical within its interior. The door may be connected to the housing and may be movable between an open position and a closed position. In the closed position, the door may completely enclose the chamber of the housing. The device may further include a fluidic cassette having a spike and a metering device. The storage device may be secured to the fluidic cassette such that the spike is inserted into the container to fluidly connect the metering device to the container. The metering device may be connected to an infusion set used to inject a dose of the radiopharmaceutical. The infusion set, the storage device, and the fluidic cassette may be held within the waste container.

[0026] In some embodiments or aspects of the disclosure, the cart may include at least one indicator associated with the storage compartment to indicate whether any of the one or more waste containers have been stored for a preselected storage period such that radioactive components of the used therapeutic or diagnostic agents decay to a preselected safety threshold level. The cart may include wheels having wheel locks configured to prevent unauthorized or unintended movement of the cart. The wheel lock may be an electronic lock in communication with the controller. The wheel lock may be a mechanical lock having a key or other mechanical locking mechanism. The wheel lock may be operatively connected to the lockable door such that the wheels are unlocked and can roll only after the lockable door is unlocked.

[0027] In some embodiments or aspects of the disclosure, a method for manufacturing and delivery of a therapeutic or diagnostic agent is provided that may include filling a container with the therapeutic or diagnostic agent, placing the container in a chamber of a storage device having a housing, closing the storage device such that the housing completely encloses the container in the chamber, shipping the storage device to an administration facility, opening a door of the storage device using an access mechanism of a delivery system, disinfecting an access port of the container using a disinfection mechanism of the delivery system, and accessing the therapeutic or diagnostic agent in the container through the access port using the delivery system.

[0028] In some embodiments or aspects of the present disclosure, accessing the therapeutic or diagnostic agent may include penetrating an access port using a spike of a cassette connected to the storage device. The method may further include reading a label or tag on the storage device to determine at least one of product information, production information, prescription information, and shipping condition information. The method may further include disinfecting the access port by emitting ultraviolet light or ejecting a disinfecting substance.

[0029] In some embodiments or aspects of the present disclosure, a method is provided for storing and disposing of used therapeutic or diagnostic agents. The method may include collecting a storage device that holds the container with the remaining portion of the therapeutic or diagnostic agent, a cassette to which the storage device is fluidly connected, and an infusion set for placement in a disposal container. The method may further include applying a label, tag, or other indicia on the disposal container to indicate a date of use, placing the disposal container with the storage device, cassette, and infusion set therein in a storage compartment, and indicating that the disposal container is safe for disposal after a preselected decay period has elapsed. The method may further include reading the label or other indicia to determine at least one of product information, production information, prescription information, and shipping condition information.

[0030] In some embodiments or aspects of the disclosure, a method is provided for delivering a dose of a therapeutic or diagnostic agent that may include inserting the therapeutic or diagnostic agent into a container, placing the container in a chamber of a storage device having a housing, closing a door of the storage device such that the housing completely encloses the container in the chamber to protect radiation emitted by the radiopharmaceutical from emitting from the housing for transport and storage of the radiopharmaceutical, determining a dose of the radiopharmaceutical for a patient based on manufacturing information of the radiopharmaceutical contained in the storage device, and unlocking the door of the storage device and opening the housing to access the radiopharmaceutical in the container and inject the determined dose into the patient.

[0031] In some embodiments or aspects of the present disclosure, accessing the therapeutic or diagnostic agent may include piercing an access port of the container using a spike of a cassette connected to the storage device. The method may further include reading a label or tag on the storage device to determine at least one of product information, production information, prescription information, and shipping condition information. The method may further include sanitizing the access port of the container. Sanitizing the access port may include emitting ultraviolet light or expelling a sanitizing substance.

[0032] Additional embodiments or aspects of the systems and methods described herein are detailed in one or more of the following sections.

[0033] Item 1: A storage device configured to connect to a delivery system for delivering a therapeutic or diagnostic agent, the storage device comprising: a housing having a chamber defined therein; a container disposed within the chamber, the container having an interior defined therebetween and a distal end opposite a proximal end configured to receive a therapeutic or diagnostic agent, the proximal end having an access port for accessing the interior; a door associated with the housing, the door being movable relative to the housing between a closed position and an open position, where in the closed position the door covers an opening in the housing to enclose the chamber of the housing and in the open position the door exposes the opening in the housing for accessing the access port of the container; and a holder in contact with the container to secure the container relative to the housing such that the access port of the container is disposed in the opening of the housing, the door being movable between the closed position and the open position in response to actuation by an access mechanism of the delivery system.

[0034] Item 2: The storage device of item 1, wherein the holder comprises a contact element for contacting the distal end of the container and a plurality of tabs connected to the contact element and configured to engage an inner surface of the housing to secure the distal end of the container to the housing.

[0035] Item 3: The storage device of item 1 or 2, further comprising a plurality of ribs within the chamber of the housing surrounding the opening, the plurality of ribs configured to secure the proximal end of the container to the housing.

[0036] Item 4: A storage device according to any one of items 1 to 3, further comprising a lock for locking the door in one of an open and closed position.

[0037] Item 5: The storage device of any one of items 1 to 4, further comprising a door cover connected to the housing, the door cover enclosing the door within the door chamber.

[0038] Item 6: A storage device described in any one of items 1 to 5, wherein the door cover comprises a door access opening having a seal and a container access opening disposed opposite the housing opening.

[0039] Item 7: The storage device of item 6, wherein the seal is penetrable by an access mechanism of a delivery system.

[0040] Item 8: A storage device described in any one of items 1 to 7, further comprising a label or tag on the housing containing machine-readable, verifiable data including at least one of product information, production information, prescription information, and shipping condition information.

[0041] Item 9: A storage device described in any one of items 1 to 8, wherein the opening in the housing is configured to receive a spike that extends into the access port to access the therapeutic or diagnostic agent when the door is in the open position.

[0042] Item 10: The storage device of any one of items 1 to 9, wherein the therapeutic or diagnostic agent is a radiopharmaceutical and the housing comprises a shield configured to prevent radiation from the radiopharmaceutical from emitting from the housing.

[0043] Item 11: An assembly configured to connect to a delivery system for delivering a therapeutic or diagnostic agent, the assembly comprising: a storage device containing the therapeutic or diagnostic agent; and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, the storage device comprising: a housing having a chamber defined therein; a container disposed within the chamber, the container having an interior configured to receive the therapeutic or diagnostic agent and an access port for accessing the interior; and a door associated with the housing, the door being movable relative to the housing between a closed position and an open position, wherein in the closed position the door is in communication with the housing. an opening in the housing to enclose the chamber, the door covering the opening in the housing in an open position, the door exposing the opening in the housing for accessing the access port of the container; and a fluid cassette comprising a spike, a metering device, and a fluid path set fluidly connecting the spike to the metering device; and an enclosure enclosing the spike, the metering device, and the fluid path set, the storage device and the fluid cassette being configured to connect to a delivery system such that the door of the storage device is accessible by an access mechanism of the delivery system and such that the spike and the metering device of the fluid cassette are accessible by a delivery mechanism of the delivery system.

[0044] Item 12: An assembly as described in item 11, wherein the container access member of the fluid cassette is insertable into the access port of the container when the door is moved to an open position to fluidly connect the metering device to the container via the fluid path set.

[0045] Item 13: An assembly described in items 11 or 12, wherein the fluid path set comprises one or more valves operable by a delivery mechanism of the delivery system to regulate fluid flow through the fluid path elements.

[0046] Item 14: An assembly according to any one of items 11 to 13, wherein the fluid cassette is connectable to a source of saline.

[0047] Item 15: An assembly according to any one of items 11 to 14, wherein the storage device comprises a guide mechanism configured to position the storage device in a desired orientation relative to the fluidic cassette.

[0048] Item 16: An assembly as described in Item 15, wherein the guide mechanism comprises one or more geometric features on the storage device, the one or more geometric features being configured to mate with corresponding one or more geometric features on the fluid cassette.

[0049] Item 17: An assembly described in any one of items 11 to 16, wherein the outlet of the metering device of the fluid cassette is configured to connect to an infusion set to deliver a dose of a therapeutic or diagnostic agent from the container to the infusion set.

[0050] Item 18: The assembly of any one of items 11 to 17, further comprising a label or tag on the housing containing machine-readable, verifiable data including at least one of product information, production information, prescription information, and shipping condition information.

[0051] Item 19: The assembly of any one of items 11 to 18, wherein the therapeutic or diagnostic agent is a radiopharmaceutical and the housing comprises a shield configured to prevent radiation from the radiopharmaceutical from emitting from the housing.

[0052] Clause 20: A delivery system for delivering a therapeutic or diagnostic agent, the delivery system comprising: an injector having a delivery mechanism and an access mechanism; and a fluid delivery assembly removably connectable to the injector, the fluid delivery assembly comprising a storage device containing the therapeutic or diagnostic agent and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, the storage device comprising a housing having a chamber defined therein; a container disposed within the chamber, the container having an interior configured to receive the therapeutic or diagnostic agent and an access port for accessing the interior; and a door associated with the housing, the door having a closed position and an open position. and a door movable relative to the housing via an access mechanism of the injector between a closed position, the door covering an opening in the housing to enclose a chamber of the housing, and in an open position, the door exposing the opening in the housing for accessing an access port of the container; the fluid cassette comprising a container access member, a metering device, and a fluid path set fluidly connecting the container access member to the metering device, and an enclosure enclosing the container access member, the metering device, and the fluid path set, the container access member and the metering device of the fluid cassette are accessible by a delivery mechanism of the injector to fluidly connect an interior of the container with the metering device via the fluid path set.

[0053] Item 21: The delivery system of item 20, further comprising an injector controller configured to determine a dose of therapeutic or diagnostic agent to be drawn from the container into the metering device based on machine-readable authentication data on the storage device.

[0054] Item 22: The delivery system of item 21, wherein the injector controller is further configured to determine a dose of therapeutic or diagnostic agent to be drawn from the container into the metering device based on at least one patient parameter.

[0055] Item 23: A delivery system according to item 21 or 22, wherein the injector controller is connected to a hospital network system.

[0056] Item 24: A delivery system according to any one of items 21 to 23, wherein the injector controller comprises multiple dosing algorithms for different predefined therapeutic or diagnostic procedures.

[0057] Item 25: A delivery system described in any one of items 20 to 24, wherein the fluid path set comprises one or more valves operable by a delivery mechanism of the delivery system to regulate fluid flow through the fluid path elements.

[0058] Item 26: A delivery system according to any one of items 20 to 25, wherein the fluid cassette is connectable to a saline source.

[0059] Item 27: A delivery system described in any one of items 20 to 26, wherein the outlet of the metering device of the fluid cassette is configured to connect to an infusion set to deliver a dose of a therapeutic or diagnostic agent from the container to the infusion set.

[0060] Item 28: A delivery system according to any one of items 20 to 27, wherein the storage device is configured to be removably or non-removably connectable to the fluidic cassette.

[0061] Item 29: The delivery system of any one of items 20 to 28, further comprising a label or tag on the housing containing machine-readable, verifiable data including at least one of product information, production information, prescription information, and shipping condition information.

[0062] Item 30: A delivery system according to any one of items 20 to 29, wherein the therapeutic or diagnostic agent is a radiopharmaceutical and the housing comprises a shield configured to prevent radiation from the radiopharmaceutical from emitting from the housing.

[0063] Item 31: An inventory device for managing the storage and disposal of used therapeutic or diagnostic agents, the inventory device comprising: a cart having a storage compartment accessible via a lockable door, the storage compartment configured to store one or more waste containers, each waste container comprising: a housing having a chamber defined therein; a container disposed within the chamber of the housing, the container configured to store a radiopharmaceutical therein; and a door connected to the housing, the door being movable between an open position and a closed position, where in the closed position the door completely surrounds the chamber of the housing; and a fluid cassette comprising a container access member and a metering device, the storage device secured to the fluid cassette such that the container access member is inserted into the container to fluidly connect the metering device to the container, the metering device being connected to an infusion set used to inject a dose of the radiopharmaceutical; and the infusion set, the storage device and the fluid cassette are retained within the waste container.

[0064] Item 32: The inventory device of item 31, wherein the cart comprises at least one indicator associated with the storage compartment to indicate whether any of the one or more waste containers have been stored for a preselected storage period such that radioactive components of the used therapeutic or diagnostic agents decay to a preselected safety threshold level.

[0065] Item 33: The inventory device of item 31 or 32, wherein the cart is provided with wheels having wheel locks configured to prevent unauthorized movement of the cart.

[0066] Item 34: The inventory device of item 33, wherein the wheel lock is an electronic lock that communicates with the controller.

[0067] Item 35: An inventory device according to item 33 or 34, wherein the wheel lock is a mechanical lock having a key or other mechanical locking mechanism.

[0068] Clause 36: An inventory device as described in any one of clauses 33 to 35, wherein the wheel lock is operatively connected to the lockable door such that the wheels are unlocked and can roll only after the lockable door is unlocked.

[0069] Item 37: A method for manufacturing and delivery of a therapeutic or diagnostic agent, the method comprising the steps of filling a container with the therapeutic or diagnostic agent, placing the container in a chamber of a storage device having a housing, closing the storage device such that the housing completely encloses the container in the chamber, shipping the storage device to an administration facility, opening a door of the storage device using an access mechanism of a delivery system, disinfecting an access port of the container using a disinfection mechanism of the delivery system, and accessing the therapeutic or diagnostic agent in the container through the access port using the delivery system.

[0070] Clause 38: The method of clause 37, wherein the step of accessing the therapeutic or diagnostic agent comprises penetrating an access port using a container access member of a cassette connected to the storage device.

[0071] Item 39: The method of items 37 or 38, further comprising reading a label or tag on the storage device to determine at least one of product information, production information, prescription information, and shipping terms information.

[0072] Clause 40: The method of any one of clauses 37 to 39, wherein the step of disinfecting the access port includes the step of emitting ultraviolet light or discharging a disinfecting substance.

[0073] Item 41: A method for storing and disposing of used therapeutic or diagnostic agents, the method comprising the steps of: collecting a storage device that holds the container with the remaining portion of the therapeutic or diagnostic agent, a cassette to which the storage device is fluidly connected, and an infusion set for placement in a waste container; applying a label, tag, or other indicia on the waste container to indicate a date of use; placing the waste container with the storage device, cassette, and infusion set therein in a storage compartment; and indicating that the waste container is safe for disposal after a preselected decay period has elapsed.

[0074] Item 42: The method of item 41, further comprising reading a label, tag, or other indicia to determine at least one of product information, production information, prescription information, and shipping terms information.

[0075] Clause 43: A method of delivering a dose of a therapeutic or diagnostic agent, the method comprising the steps of inserting the therapeutic or diagnostic agent into a container, placing the container in a chamber of a storage device having a housing, closing a door of the storage device such that the housing completely encloses the container in the chamber to protect radiation emitted by the radiopharmaceutical from emitting from the housing for transport and storage of the radiopharmaceutical, determining a dose of the radiopharmaceutical for a patient based on manufacturing information of the radiopharmaceutical contained in the storage device, and unlocking the door of the storage device and opening the housing to access the radiopharmaceutical in the container and inject the determined dose into the patient.

[0076] Item 44: The method of item 43, wherein the step of accessing the therapeutic or diagnostic agent comprises penetrating an access port using a container access member of a cassette connected to the storage device.

[0077] Item 45: The method of items 43 or 44, further comprising reading a label or tag on the storage device to determine at least one of product information, production information, prescription information, and shipping terms information.

[0078] Item 46: The method of any one of items 43 to 45, further comprising disinfecting an access port of the container.

[0079] Clause 47: The method of clause 46, wherein the step of disinfecting the access port includes the step of emitting ultraviolet light or expelling a disinfecting substance.

[0080] Clause 48: A storage device configured to connect to a delivery system, the storage device comprising: a housing having a chamber defined therein; a container disposed within the chamber, the container housing a radiopharmaceutical therein, the radiopharmaceutical being a therapeutically or prophylactically effective amount of a free metal cation of the alkaline earth metal radium-223; a door associated with the housing, the door being movable relative to the housing between a closed position and an open position, wherein in the closed position the door covers an opening in the housing to enclose the chamber of the housing and in the open position the door exposes the opening in the housing for accessing the access port of the container; and a holder in contact with the container to secure the container relative to the housing such that the access port of the container is disposed in the opening of the housing, the door being movable between the closed position and the open position in response to actuation by an access mechanism of the delivery system.

[0081] Clause 49: An assembly configured to connect to a delivery system for delivering a radiopharmaceutical, the assembly comprising: a storage device containing a therapeutic or diagnostic agent; and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, the storage device comprising: a housing having a chamber defined therein; a container disposed within the chamber, the container containing a radiopharmaceutical within its interior, the radiopharmaceutical being a therapeutically or prophylactically effective amount of a free metal cation of the alkaline earth metal radium-223; and a door associated with the housing, the door being movable relative to the housing between a closed position and an open position, the door being adapted to close the chamber of the housing; and a door covering an opening in the housing to enclose the access port of the container, in an open position, the door exposing the opening in the housing for accessing the access port of the container; the fluid cassette comprising a container access member, a metering device, and a fluid path set fluidly connecting the container access member to the metering device; and an enclosure enclosing the container access member, the metering device, and the fluid path set, wherein the storage device and the fluid cassette are configured to connect to a delivery system such that the door of the storage device is accessible by an access mechanism of the delivery system and such that the container access member and the metering device of the fluid cassette are accessible by a delivery mechanism of the delivery system.

[0082] Clause 50: A delivery system for delivering a therapeutic or diagnostic agent, the delivery system comprising an injector having a delivery mechanism and an access mechanism, and a fluid delivery assembly removably connectable to the injector, the fluid delivery assembly comprising a storage device containing the therapeutic or diagnostic agent, and a fluid cassette fluidly connectable to the storage device for accessing the therapeutic or diagnostic agent, the storage device comprising a housing having a chamber defined therein, a container disposed within the chamber of the housing, the container housing a radiopharmaceutical within its interior, the radiopharmaceutical being a therapeutically or prophylactically effective amount of the free metal cation of the alkaline earth metal radium-223, and a door associated with the housing, the door being movable relative to the housing via the access mechanism of the injector between a closed position and an open position, the door covering an opening of the housing to surround the chamber of the housing, and the door covering the access of the container to the chamber of the housing, the door covering the opening of the housing to surround the chamber of the housing, and the door covering the access of the container to the chamber of the housing. and a door exposing an opening in the housing to access the port, the fluid cassette comprising a container access member, a metering device, and a fluid pathway set fluidly connecting the container access member to the metering device, and an enclosure enclosing the container access member, the metering device, and the fluid pathway set, the container access member and the metering device of the fluid cassette are accessible by a delivery mechanism of the injector to fluidly connect an interior of the container with the metering device via the fluid pathway set, the injector comprising an injector controller configured to determine a dose of the radiopharmaceutical based on manufacturing data attached to the housing of the storage device, the injector controller being communicatively connected to the injector to control the injector to inject the dose such that the injection amount received by the patient is the dose determined by the injector controller based on the manufacturing data attached to the housing of the storage device.

[0083] Item 51: An inventory device for managing the storage and disposal of used radiopharmaceuticals, the inventory device comprising: a cart having shelves accessible via a lockable door, the shelves configured to store waste containers, each waste container comprising: a storage device comprising: a housing having a chamber defined therein; a receptacle disposed within the chamber of the housing, the receptacle configured to store a radiopharmaceutical within its interior; and a door connected to the housing, the door movable between an open position and a closed position, the door completely enclosing the chamber of the housing in the closed position. and a fluid cassette comprising a storage device, a container access member and a metering device, the storage device secured to the fluid cassette such that the container access member is inserted into the container to fluidly connect the metering device to the container, the metering device being connected to an infusion set used to inject a dose of the radiopharmaceutical, the infusion set, the storage device and the fluid cassette being retained within a waste container, the cart comprising an indicator for the shelf to indicate which waste container has been stored for a preselected storage period such that the radiopharmaceutical will decay to below a preselected safety threshold level of the radioactivity of the substance.

[0084] Item 52: A method for the manufacture and delivery of a radiopharmaceutical for targeted radionuclide therapy or diagnostic imaging services, the method comprising the steps of: filling a container with a radiopharmaceutical for TRT or diagnostic imaging services, the radiopharmaceutical being a therapeutically or prophylactically effective amount of a free metal cation of the alkaline earth metal radium-223; placing the container in a chamber of a storage device having a housing; closing the storage device such that the housing completely encloses the container in the chamber; shipping the storage device to an administration facility; opening a door of the storage device using an access mechanism of a delivery system; disinfecting an access port of the container using a disinfection mechanism of the delivery system; and accessing the radiopharmaceutical in the container through the access port using the delivery system.

[0085] Item 53: A method for storage and disposal of radiopharmaceuticals used in targeted radionuclide therapy or diagnostic imaging services, the method comprising the steps of: collecting a storage device that holds the container with the remainder of the radiopharmaceutical, a cassette to which the storage device is fluidly connected, and an infusion set for placement in a waste container; applying a label, tag, or other indicia on the waste container to indicate the date of use; placing the waste container with the storage device, cassette, and infusion set therein in a storage compartment; and indicating that the waste container is safe for disposal after a preselected decay period has elapsed, wherein the radiopharmaceutical is a therapeutically or prophylactically effective amount of the free metal cation of the alkaline earth metal radium-223.

[0086] Clause 54: A method for injecting a dose of targeted radionuclide therapy or diagnostic imaging services, the method comprising the steps of: inserting a radiopharmaceutical into a container, the radiopharmaceutical being a therapeutically or prophylactically effective amount of free metal cation of the alkaline earth metal radium-223; placing the container in a chamber of a storage device having a housing; closing a door of the storage device such that the housing completely encloses the container in the chamber to protect radiation emitted by the radiopharmaceutical from emitting from the housing for transport and storage of the radiopharmaceutical; determining a dose of the radiopharmaceutical for a patient based on manufacturing information of the radiopharmaceutical contained in the storage device; and unlocking the door of the storage device and opening the housing to access the radiopharmaceutical in the container and inject the determined dose into the patient.

[0087] Item 55: A radiopharmaceutical administration infusion system for a therapeutically or prophylactically effective amount of free metal cation of radium-223 according to any one of the preceding items.

[0088] Item 56: An inventory device for the management, storage and disposal of a therapeutically or prophylactically effective amount of free metal cation of radium-223 according to any one of the preceding items.

[0089] Item 57: The method of any one of the preceding items, further comprising a therapeutically or prophylactically effective amount of free metal cation of radium-223.

[0090] In view of the above, there is also a need for devices, systems, and methods for improved delivery and filtration of radiopharmaceuticals. Additionally, there is a need for a system for delivering radiopharmaceuticals that can be safely performed by a wider range of medical professionals than is currently possible or permitted by regulatory agencies. Embodiments of the present disclosure may improve upon conventional radiopharmaceutical injection systems and methods in many ways. Embodiments of the present disclosure may reduce radiation exposure to the patient and operator and provide the operator with more awareness of the dose, dose rate, and associated radiation associated with the injection procedure. Embodiments of the present disclosure may mitigate adverse treatment outcomes by automatically and reliably detecting and correcting conditions such as faulty doses, radiopharmaceutical retention, extravasation, system leaks, and fluid line occlusions. Additionally, embodiments of the present disclosure may automatically perform test injections to identify these conditions before delivering the full dose of radiopharmaceutical. Embodiments of the present disclosure may also minimize the number of component connections made or disconnected before, during, and / or after the procedure to reduce possible contamination and leak points. Embodiments of the present disclosure may effectively isolate and store radioactive waste for later disposal. The embodiments of the present disclosure may also reduce supply chain concerns due to the way radiopharmaceuticals are delivered and removed from the system after use. As a corollary to improved patient outcomes, the advantages of the present disclosure may also reduce the burden on hospital staff in complying with various regulatory burdens, as many regulatory concerns may be automatically addressed by the embodiments of the present disclosure. The embodiments of the present disclosure may provide remote access to experienced and / or licensed personnel, such as authorized users, to allow remote personnel to oversee or operate drug preparation and delivery to meet legal requirements. This may allow more sites and more operators to deliver drugs, thus expanding patient access to drugs. The embodiments of the present disclosure may also perform some of the necessary record keeping and data analysis and exchange functions. With this background in mind, the embodiments of the present disclosure are directed to a fluid injection system.

[0091] In some embodiments or aspects of the present disclosure, the present disclosure is directed to various fluid injection delivery systems.

[0092] Additional embodiments or aspects of such fluid injection delivery systems described herein are detailed in one or more of the following sections:

[0093] Item 1': A fluid injection delivery system comprising: at least one fluid reservoir comprising a first fluid reservoir configured to receive a radiopharmaceutical; a radiation filter in fluid communication with the at least one fluid reservoir, the radiation filter configured to retain radioactive particles from the radiopharmaceutical that pass through the radiation filter; at least one sensor configured to detect radioactivity in at least one of the first fluid reservoir, the radiation filter, and fluid path elements in fluid communication with the radiation filter; and a controller in operative communication with the at least one sensor, the controller programmed or configured to receive radioactivity measurements from the at least one sensor and determine based on the radioactivity measurements that an amount of radioactive particles in at least one of the first fluid reservoir, the radiation filter, and the fluid path elements meets a predetermined threshold.

[0094] Item 2': The fluid injection delivery system of item 1', wherein the predetermined threshold includes at least one of a predetermined prescribed dose of the radiopharmaceutical, a predetermined safe dose of the radiopharmaceutical, a predetermined residence volume, a predetermined rate of change of radioactivity relative to the volume of fluid moved through the filter, and a predetermined rate of change of radioactivity over time.

[0095] Item 3': A fluid injection delivery system as described in items 1' or 2', wherein the controller is further programmed or configured to determine a cumulative amount of the radiopharmaceutical injected from the first fluid reservoir based on the radioactivity measurements and one or more injection parameters.

[0096] Clause 4': The fluid injection delivery system of clause 3', wherein the one or more injection parameters include at least one of: an injection rate of the radiopharmaceutical, an injection volume of the radiopharmaceutical, an injection duration of the radiopharmaceutical, a half-life of the radiopharmaceutical, a decay series of the radiopharmaceutical, an age of the radiopharmaceutical, a total volume of the radiopharmaceutical, a concentration of the radiopharmaceutical, and an initial activity of the radiopharmaceutical.

[0097] Item 5': The fluid injection delivery system of item 3', wherein the controller is further programmed or configured to compare the cumulative amount of injected radiopharmaceutical with a predetermined prescribed dosage.

[0098] Item 6': The fluid injection delivery system of item 3', wherein the controller is further programmed or configured to adjust the injection rate of the radiopharmaceutical based on a cumulative amount of the radiopharmaceutical injected.

[0099] Item 7': The fluid injection delivery system of item 3', wherein the controller is further programmed or configured to stop the injection procedure in response to the cumulative amount of injected radiopharmaceutical meeting a predetermined threshold.

[0100] Clause 8': A fluid injection delivery system as described in clauses 1' to 7', wherein the controller is further programmed or configured to determine a residual level of radioactive particles within the radiation filter or within the fluid path set based on radioactivity measurements received from at least one sensor.

[0101] Item 9': A fluid injection delivery system as described in items 1' to 8', wherein the controller is further programmed or configured to determine that the radiopharmaceutical is chelated based on radioactivity measurements received from at least one sensor.

[0102] Clause 10': A fluid injection delivery system as described in clauses 1' to 9', wherein the at least one sensor comprises a first sensor associated with a fluid path set upstream of the radiation filter and a second sensor associated with a fluid path set downstream of the radiation filter, and the controller is programmed or configured to determine the amount of radioactive particles retained by the radiation filter by comparing a radioactivity measurement from the first sensor with a radioactivity measurement from the second sensor.

[0103] Clause 11': A fluid injection delivery system as described in clauses 1' to 10', wherein the fluid pathway set includes an intermediate container in fluid communication with the at least one fluid reservoir and located downstream of the at least one fluid reservoir, at least one of the at least one sensors is associated with the intermediate container to detect radioactivity in the intermediate container, and the controller is configured to prevent delivery of a radiopharmaceutical from the intermediate container to the patient based on an amount of radioactive particles in the intermediate container that deviates from a predetermined threshold.

[0104] Item 12': A fluid injection delivery system described in items 1' to 11', wherein the at least one fluid reservoir further comprises an additional fluid reservoir configured to inject a flushing agent.

[0105] Item 13': A fluid injection delivery system as described in items 1' to 12', wherein the at least one fluid reservoir further comprises an additional fluid reservoir configured to inject another medicinal drug.

[0106] Item 14': The fluid injection delivery system according to item 13', wherein the other pharmaceutical agent is a protective agent.

[0107] Item 15': A fluid injection delivery system according to items 1' to 14', wherein the first fluid reservoir comprises a radiopharmaceutical generator.

[0108] Clause 16': A fluid injection delivery system as described in clauses 1' to 15', wherein the first fluid reservoir comprises a housing having a chamber defined therein, a container disposed within the chamber, the container having an interior defined therebetween and a distal end opposite a proximal end configured to receive a radiopharmaceutical, the proximal end having an access port for accessing the interior, a door associated with the housing, the door being movable relative to the housing between a closed position and an open position, wherein in the closed position the door covers an opening of the housing to surround the chamber of the housing, and in the open position the door exposes the opening of the housing for accessing the access port of the container, and a holder that contacts the container to fix the container relative to the housing such that the access port of the container is positioned in the opening of the housing within the chamber of the housing, and the door of the first fluid reservoir is movable between the closed position and the open position in response to actuation by an access mechanism of the fluid injection delivery system.

[0109] Clause 17': A filtration system for a radiopharmaceutical fluid injection system, the filtration system comprising: a radiation filter in fluid communication with at least one fluid reservoir of the radiopharmaceutical fluid injection system, the radiation filter configured to retain radioactive particles from the radiopharmaceutical received from the radiopharmaceutical fluid injection system; at least one sensor configured to detect radioactivity in at least one of the fluid reservoir, the radiation filter, and a set of fluid paths in fluid communication with the radiation filter; and a controller in operative communication with the at least one sensor, the controller programmed or configured to receive radioactivity measurements from the at least one sensor and determine based on the radioactivity measurements that an amount of radioactive particles in at least one of the fluid reservoir, the radiation filter, and the set of fluid paths meets a predetermined threshold.

[0110] Item 18': A fluid injection system comprising: at least one fluid reservoir comprising a first fluid reservoir configured to inject a radiopharmaceutical; a fluid path set in communication with the at least one fluid reservoir, the fluid path set comprising one or more fluid path elements including a catheter configured to be inserted into an intravenous administration site of the patient; a patient sensor configured to detect radioactivity in a patient associated with the intravenous administration site; and a controller in operative communication with the patient sensor and the fluid path set, the controller programmed or configured to receive radioactivity measurements from the patient sensor and determine the presence or absence of retention of the radiopharmaceutical in the patient based on the radioactivity measurements from the patient sensor.

[0111] Item 19': The fluid injection system of item 18', further comprising a fluid pathway set sensor configured to detect radioactivity in the fluid pathway set upstream of the intravenous administration site.

[0112] Item 20': The fluid injection system of item 18' or 19', wherein the controller is further programmed or configured to modify or stop the injection procedure in response to determining the presence of a retention.

[0113] Item 21': A fluid injection system described in any one of items 18' to 20', wherein the controller is further programmed or configured to determine retention of a radiopharmaceutical associated with an intravenous administration site based on radioactivity measurements from the patient sensor and the fluid pathway set sensor.

[0114] Clause 22': A fluid injection system as described in any one of clauses 19' to 21', wherein the at least one fluid reservoir further comprises a second fluid reservoir configured to inject a flushing agent, and the controller is programmed or configured to increase injection of the flushing agent in response to determining retention of the radiopharmaceutical at the intravenous administration site.

[0115] Clause 23': A fluid injection system described in any one of clauses 19' to 21', wherein the controller is further programmed or configured to determine a leak in the fluid path set based on a comparison of radioactivity measurements from the patient sensor and the fluid path set sensor.

[0116] Clause 24': A fluid injection system described in any one of clauses 19' to 21', wherein the controller is further programmed or configured to determine an occlusion in the fluid pathway set based on a comparison of radioactivity measurements from the patient sensor and the fluid pathway set sensor.

[0117] Clause 25': A fluid injection system as described in any one of clauses 18' to 24', further comprising an interrogation sensor configured to detect radioactivity in the patient away from the intravenous administration site, wherein the controller is programmed or configured to receive radioactivity measurements from the interrogation sensor and determine the presence or absence of retention of the radiopharmaceutical in the patient based on a comparison of the radioactivity measurements from the patient sensor and the interrogation sensor.

[0118] Clause 26': A retention detection system for a radiopharmaceutical fluid injection system, the retention detection system comprising: a patient sensor configured to detect radioactivity in a patient adjacent to an intravenous administration site on the patient; a fluid pathway set sensor configured to detect radioactivity in a fluid pathway set of the fluid injection system upstream of the intravenous administration site; and a controller in operative communication with the patient sensor and the fluid pathway set sensor, the controller being programmed or configured to receive radioactivity measurements from the patient sensor and the fluid pathway set sensor and to determine the presence or absence of retention of a radiopharmaceutical in the patient based on the radioactivity measurements from the patient sensor and the fluid pathway set sensor.

[0119] Further details and advantages of the various examples detailed herein will become apparent from a consideration of the following detailed description of the various examples in conjunction with the accompanying drawings. [Brief description of the drawings]

[0120] [Figure 1] FIG. 1 is a schematic diagram depicting a conventional supply chain for radiotherapeutic agents adapted for use with TRT, according to the prior art. [Diagram 2] FIG. 1 is a schematic diagram depicting a conventional method for administration of TRT according to the prior art. [Diagram 3] FIG. 1 is a schematic diagram depicting an improved supply chain of a radiotherapeutic agent configured for use with TRT, according to some embodiments or aspects of the present disclosure. [Figure 4] FIG. 1 is a schematic diagram depicting an improved method for administration of TRT, according to some embodiments or aspects of the present disclosure. [Diagram 5] FIG. 1 is a perspective view of a system for the delivery, administration, and disposal of liquid products requiring precise volumetric delivery from a controlled source, according to some embodiments or aspects of the present disclosure. [Figure 6] FIG. 1 is a perspective view of a system for the delivery, administration, and disposal of liquid products requiring precise volumetric delivery from a controlled source, according to some embodiments or aspects of the present disclosure. [Figure 7] FIG. 1 illustrates a perspective view of a storage device for storing a liquid product, such as a radiotherapeutic agent, according to some embodiments or aspects of the present disclosure. [Figure 8] FIG. 8 is a cross-sectional perspective view of the storage device shown in FIG. 7. [Figure 9] FIG. 8 is an exploded top perspective view of the storage device shown in FIG. 7. [Figure 10] FIG. 2 is a cross-sectional perspective view of the storage device shown with a first container. [Figure 11] FIG. 2 is a cross-sectional perspective view of the storage device shown with a second container. [Figure 12] FIG. 13 is a detailed perspective view of a security cover on an access door of a storage device according to some embodiments or aspects of the present disclosure. [Figure 13] FIG. 13 is a detailed view of a locking mechanism for preventing reuse of a storage device, according to some embodiments or aspects of the present disclosure. [Figure 14] FIG. 13 is a detailed view of a locking mechanism for preventing reuse of a storage device, according to some embodiments or aspects of the present disclosure. [Figure 15] FIG. 1 illustrates a perspective view of a storage device for storing a liquid product, such as a radiotherapeutic agent, according to some embodiments or aspects of the present disclosure. [Figure 16] FIG. 16 is a side view of the storage device shown in FIG. [Figure 17A] FIG. 1 illustrates a bottom perspective view of a storage device according to some embodiments or aspects of the present disclosure. [Figure 17B] FIG. 1 illustrates a bottom perspective view of a storage device according to some embodiments or aspects of the present disclosure. [Figure 18] FIG. 16 is an exploded perspective view of the storage device shown in FIG. [Figure 19] FIG. 16 is a cross-sectional perspective view of the storage device shown in FIG. [Figure 20] FIG. 1 illustrates a perspective view of a storage device and a fluidic cassette for administering doses from the storage device, according to some embodiments or aspects of the present disclosure. [Figure 21] FIG. 21 is a perspective view of the fluidic cassette shown in FIG. 20. [Figure 22] FIG. 22 is an exploded perspective view of the fluidic cassette shown in FIG. 21. [Figure 23] FIG. 13 is a perspective view of a receptacle access member configured to penetrate a receptacle of a storage device according to some embodiments or aspects of the present disclosure. [Figure 24] FIG. 13 is a detailed perspective view of a metering device connection interface of a fluidic cassette according to some embodiments or aspects of the present disclosure. [Figure 25A] FIG. 13 is a perspective view of the plunger cap shown in the unlocked position. [Figure 25B] FIG. 25B is a perspective view of the plunger cap of FIG. 25A shown in the locked position. [Figure 26] FIG. 1 is a perspective view of a fluidic cassette and components of a delivery system configured to interact with the fluidic cassette, according to some embodiments or aspects of the present disclosure. [Figure 27] FIG. 1 illustrates a perspective view of a storage device and a fluidic cassette for administering doses from the storage device, according to some embodiments or aspects of the present disclosure. [Figure 28] FIG. 28 is a detailed view of the connection between the storage device and the fluidic cassette shown in FIG. 27. [Figure 29] FIG. 29 is a perspective view of the fluidic cassette shown in FIG. 28. [Diagram 30] FIG. 30 is an exploded perspective view of the fluidic cassette shown in FIG. 29. [Diagram 31] 1 is a schematic diagram of a fluid connection between a container of a storage device, a fluid cassette, and a patient delivery line, according to some embodiments or aspects of the present disclosure. [Diagram 32] FIG. 1 is a perspective view of a fluidic cassette and storage device and components of an infusion system configured to interact with the fluidic cassette and storage device, according to some embodiments or aspects of the present disclosure. [Diagram 33] FIG. 33 is a perspective view of the components of the infusion system shown in FIG. [Diagram 34] FIG. 1 illustrates a perspective view of a disinfection system for disinfecting a portion of a storage device according to some embodiments or aspects of the present disclosure. [Diagram 35] FIG. 1 is a perspective view of a carrier tray for transporting multiple storage devices according to some embodiments or aspects of the present disclosure. [Diagram 36] FIG. 13 is a perspective view of a disposal container for disposing of storage devices and cassettes according to some embodiments or aspects of the present disclosure. [Figure 37] FIG. 1 is a schematic diagram of a storage enclosure for storing multiple waste containers, according to some embodiments or aspects of the present disclosure. [Figure 38] FIG. 13 is a flow diagram of a patency check procedure according to some embodiments or aspects of the present disclosure. [Figure 39] FIG. 1 is a flow diagram of an administration procedure using the described system, according to some embodiments or aspects of the present disclosure. [Diagram 40]1 is a schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Diagram 41] 41 is a graph of radiation sensor output during an injection procedure performed by the system of FIG. 40. [Diagram 42] 1 is a partial schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Diagram 43] 1 is a partial schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Diagram 44] 1 is a schematic diagram of a fluid injection system according to an embodiment of the present disclosure. [Diagram 45] 1 is a schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Diagram 46] 1 is a schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Figure 47] 1 is a schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Figure 48] 48 is a graph of fluid flow during an injection procedure performed by the system of FIG. 47. [Figure 49] 49 is a graph of the radiation sensor output during the injection procedure of FIG. 48. [Figure 50] 48 is a graph of fluid flow during an injection procedure performed by the system of FIG. 47. [Figure 51] 51 is a graph of the radiation sensor output during the injection procedure of FIG. 50. [Figure 52] 48 is a graph of fluid flow during an injection procedure performed by the system of FIG. 47. [Diagram 53] 53 is a graph of the radiation sensor output during the injection procedure of FIG. 52. [Figure 54] 1 is a schematic diagram of a fluid injection system according to an embodiment or aspect of the present disclosure. [Figure 55] FIG. 1 is a schematic diagram of a remote control system that may be utilized in conjunction with any of the fluid injection systems of the present disclosure. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0121] In Figures 1-55, like characters may refer to the same components and elements, unless otherwise noted.

[0122] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0123] Spatial or directional terms such as "left," "right," "inner," "outer," "above," "below," and the like, relate to the embodiment or aspect as illustrated in the drawings and should not be considered as limiting, as the embodiment or aspect may assume various alternative orientations.

[0124] All numbers used in this specification and claims should be understood to be modified in all instances by the term "about." "About" means ±25% of the stated value, for example ±10% of the stated value. However, this should not be considered as limiting the analysis of values ​​under the doctrine of equivalents.

[0125] Unless otherwise indicated, all ranges or ratios disclosed herein should be understood to encompass the starting and ending values ​​and any and all subranges or subratios subsumed therein. For example, a range or ratio described as "1 to 10" should be considered to include any and all subranges or subratios between (and including) the minimum value of 1 and the maximum value of 10, i.e., all subranges or subratios beginning with a minimum value of 1 or greater and ending with a maximum value of 10 or less. Ranges and / or ratios disclosed herein represent average values ​​across the specified ranges and / or ratios.

[0126] The terms "first," "second," and the like are not intended to refer to a particular order or chronology, but rather to different conditions, characteristics, or elements.

[0127] All documents mentioned herein are "incorporated by reference" in their entirety.

[0128] The term "at least" is synonymous with "greater than or equal to."

[0129] The term "not greater than" is synonymous with "less than or equal to."

[0130] Some non-limiting embodiments or aspects may be described herein in relation to a threshold value. As used herein, meeting a threshold may refer to a value being greater than the threshold, more than the threshold, higher than the threshold, greater than or equal to the threshold, less than the threshold, less than the threshold, lower than the threshold, lower than or equal to the threshold, equal to the threshold, etc.

[0131] As used herein, "at least one of" is synonymous with "one or more of." For example, the phrase "at least one of A, B, or C" means A, B, or C, or any combination of any two or more of A, B, or C. For example, "at least one of A, B, or C" includes only A, or only B, or only C, or A and B, or A and C, or B and C, or all of A, B, and C.

[0132] The term "includes" is synonymous with "comprises."

[0133] When used in relation to a component of a fluid delivery system, such as a fluid reservoir, syringe, or fluid line, the term "distal" refers to the portion of said component closest to the patient. When used in relation to a component of an injection system, such as a fluid reservoir, syringe, or fluid line, the term "proximal" refers to the portion of said component closest to the injector of the injection system (i.e., the portion of said component furthest from the patient). When used in relation to a component of a fluid delivery system, such as a fluid reservoir, syringe, or fluid line, the term "upstream" refers to the direction away from the patient toward the injector in relation to the normal flow of fluid in the injection system. When used in relation to a component of a fluid delivery system, such as a fluid reservoir, syringe, or fluid line, the term "downstream" refers to the direction away from the injector toward the patient in relation to the normal flow of fluid in the fluid delivery system.

[0134] As used herein, the terms "communication" and "communicating" may refer to receiving, accepting, sending, forwarding, providing, etc., information (e.g., data, signals, messages, instructions, commands, etc.).

[0135] The term "radiopharmaceutical" as used herein refers to a pharmaceutical containing a radionuclide. Radiopharmaceuticals are preferably configured for intravenous (iv) administration as described herein. There are two types of radiopharmaceuticals: diagnostic (or imaging) radiopharmaceuticals and therapeutic radiopharmaceuticals, although therapeutic radiopharmaceuticals may be used for both in some cases. For example, a TRS may therefore emit gamma rays that may be used for dosimetry evaluation and / or diagnostic purposes. Radiopharmaceuticals commonly used for imaging, such as positron emitters, may also be used for therapy. See, for example, Hioki, T., Gholami, YH, McKelvey, KJ, et al., Overlooked potential of positrons in cancer therapy, Sci Rep 11, 2475 (2021).

[0136] The term "diagnostic radiopharmaceutical" or "imaging radiopharmaceutical" as used herein includes gamma-emission imaging radiopharmaceuticals for use in SPECT or SPECT / CT imaging and / or positron-emission imaging radiopharmaceuticals for use in PET or PET / CT imaging. Examples of gamma-emission imaging radiopharmaceuticals include, but are not limited to, technetium (Tc-99m), iodine (I-123), indium (In-111), gallium (Ga-67), or rhenium (Re-186). Examples of positron-emission imaging radiopharmaceuticals include, but are not limited to, fluorine (F-18), gallium (Ga-68), zirconium (Zr-89), iodine (I-124), copper (Cu-64), rubidium (Rb-82), or yttrium (Y-86).

[0137] The term "therapeutic radiopharmaceuticals" as used herein includes beta therapy radiopharmaceuticals, alpha therapy radiopharmaceuticals, positron therapy radiopharmaceuticals, Auger therapy radiopharmaceuticals, gamma therapy radiopharmaceuticals, and / or combinations thereof.

[0138] As used herein, the term "therapeutic or diagnostic agent" refers to any diagnostic, imaging, radiotherapy or chemotherapy agent, therapeutic agent, or any other liquid or powder (after reconstitution) used in a therapeutic or diagnostic capacity that requires precise dose delivery from a controlled source, where the dose is the amount of active ingredient. Dose delivery may be accomplished by precise volumetric delivery.

[0139] All radiation shielding is either fractional or partial. Adding a layer of half the thickness to a shield reduces the penetrating radiation by a factor of two. The effectiveness of a shielding depends on the energy of the radiation being shielded. Thus, terms such as "blocking," "stopping," or "preventing" radiation transmission or emission refer to the reduction of the transmitted or emitted radiation to an acceptable level. This acceptable level may depend on local regulations, requirements, policies, or preferences. Many materials used in shielding and associated guidelines are well known to those skilled in the art of health physics.

[0140] The present disclosure comprises, consists of, or consists essentially of the following examples of embodiments or aspects, in any combination.Various examples of the present disclosure can be described separately.However, it should be understood that this is merely for ease of illustration and description.In implementing the present disclosure, one or more aspects of the present disclosure described in one example can be combined with one or more aspects of the present disclosure described in one or more of the other examples.

[0141] In various embodiments or aspects, the present disclosure is directed to systems and methods for the delivery, storage, administration, and disposal of radiopharmaceutical therapeutics. The present disclosure is also directed to systems and methods for the delivery, storage, administration, and disposal of other therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source, such as chemotherapy pharmaceuticals. As described herein, conventional methods for the delivery and administration of therapeutic or diagnostic agents that require precise volumetric delivery from a controlled source significantly limit their applicability and use. After considering shipping, handling, and patient schedules, a treatment site has a limited amount of time to administer a dose to a particular patient. The systems and methods described herein provide improved delivery, storage, administration, and disposal of therapeutic or diagnostic agents that allow for longer times to administer a dose to a particular patient.

[0142] As described in various embodiments or aspects of the present disclosure, the storage device can be configured to store radiotherapeutic agents from the point of production for shipping and storage at a treatment facility, so that the radiotherapeutic agents are fully enclosed and containerized until use. Each of the storage devices can be sized, shaped, and configured to provide radiation shielding appropriate for the radioisotope and dose being stored. The storage devices can also be further packaged and surrounded by additional shielding. The housing of the storage device is configured to be opened and unsealed only at the treatment site utilizing a dedicated device, as described herein. In some embodiments or aspects, the storage device can be configured to store therapeutic or diagnostic agents other than radiopharmaceuticals from the point of production for shipping and storage at a treatment facility, so that the therapeutic or diagnostic agents are fully enclosed and containerized until use.

[0143] As described in various embodiments or aspects of the present disclosure, a system can be provided that includes a radiotherapeutic injection / infusion system that is specifically adapted to access the therapeutic or diagnostic agent stored in the storage device, such that the substance is only accessible for administration to a patient via the injection / infusion system, and administration is otherwise prevented if the storage device is not recognized as an un-tampered storage device. The storage device can be configured such that only the injection / infusion system can open the storage device and access the therapeutic or diagnostic agent to inject the agent into a patient. If the therapeutic or diagnostic agent is a radiopharmaceutical, the combination of the storage device and the injection / infusion system can help ensure that the radioactive material remains completely sealed and enclosed from the time of production until use. Furthermore, the injection / infusion system and the storage device once used can remain connected and non-openable to facilitate safe containment and disposal of radioactive waste after use.

[0144] As described in various embodiments or aspects of the present disclosure, systems and methods can be provided to calculate a dose for a particular patient based on the therapeutic or diagnostic agent being administered, patient parameters such as the patient's weight, known manufacturing and / or calibration dates, known radioactivity or other characteristics of the therapeutic or diagnostic agent at the time of manufacture, and known current date and time to determine an appropriate dose for the patient to inject a volume of the therapeutic or diagnostic agent corresponding to the calculated active dose of the agent into the patient for treatment. If the therapeutic or diagnostic agent is a radiopharmaceutical, the unused portion of the radiopharmaceutical and other components that have come into contact with the radiopharmaceutical, which may be contaminated, can be stored in a waste container for storage depending on the initial dose in the storage device until the radioactivity has decreased to an acceptable level (usually about 10 half-lives of the radioisotope). The systems and methods are configured to ensure consistency of administration in that each patient receives the desired amount of the therapeutic or diagnostic agent.

[0145] As described in various embodiments or aspects of the present disclosure, improved systems and methods are provided to ensure that stored products are no longer designed or required to be patient-specific. Instead, the systems disclosed herein are configured to administer treatment to any patient that may be present at the site on any particular day, to allow for more flexibility in how stored products can be utilized at the treatment site so that an effective amount of radiopharmaceutical can be delivered to the patient. Such patient-specific administration is achieved without the need for dose calibrators, thereby eliminating additional dose assays to prepare the patient-ready dose.

[0146] As described in various embodiments or aspects of the present disclosure, systems and methods can be provided to monitor therapeutic or diagnostic agents stored in a disposal container and indicate when the stored material has sufficiently decayed and is safe for disposal. Once that determination is made, instructions can be provided to a user (e.g., software prompts, or an LED light can be switched from red to green, or the red LED can be turned off and the green LED can be turned on) so that staff know that there is material suitable for disposal, can identify the material to be discarded, and can properly dispose of the material.

[0147] As described in various embodiments or aspects of the disclosure, the improved inventory management flexibility associated with the systems and methods described herein allows care providers to manage inventory more effectively; inventory no longer needs to be managed using a simple first-in, first-out approach and / or an approach that requires each stored dose to be provided only to a single, specific patient. Instead, inventory management and use of doses is managed to take into account various factors, including the need for patients to better manage their supply of available doses. For example, if a particular patient requires a large dose due to the patient's size (e.g., weight, height and weight, body composition, etc.), a newer, more radioactive vial of therapeutic agent can be selected to administer to the patient, such that only one vial (rather than multiple vials) is required to inject the dose into the patient. This allows for easier administration (e.g., using only one injection sequence) and provides more flexibility with respect to inventory management and administration, resulting in more efficient utilization of doses and less waste. In some circumstances, this type of flexibility may also help reduce exposure to clinicians during administration of the treatment and minimize the subsequent decontamination process after the patient has received their dose.

[0148] FIG. 3 illustrates an improved supply chain for a therapeutic or diagnostic agent according to some embodiments or aspects of the present disclosure. The therapeutic or diagnostic agent may be manufactured in bulk at a manufacturing facility. Instead of loading the therapeutic or diagnostic agent into bulk containers for shipment to a hot lab, the therapeutic or diagnostic agent is loaded into a storage device that is shipped directly to the treatment site. The storage device is configured to store the therapeutic or diagnostic agent from the point of production, during transport, and during storage at the treatment facility. The therapeutic or diagnostic agent is configured to be administered directly from the storage device to a patient using a delivery system, as described herein. The administration for each specific patient is determined by the delivery system instead of using a dose calibrator.

[0149] As shown in Figure 4, the method of diagnosing, referring, and treating a patient according to the improved supply chain eliminates multiple methods compared to the conventional method. After a patient P is diagnosed and a dose of therapeutic or diagnostic agent is prescribed based on the patient's weight, the dose can be administered using the delivery system 100 directly from the storage device 200 loaded into the delivery system 100. The prescribing and administration can be done by the same authorized user AU.

[0150] 5, a delivery system 100 for delivery, administration, and disposal of therapeutic or diagnostic agents according to some embodiments or aspects of the present disclosure is shown. As described herein, the system 100 includes several components designed to work together to provide safe, streamlined, and flexible delivery of therapeutic or diagnostic agents. The delivery system 100 is further configured to help end users maintain and manage their inventory of therapeutic or diagnostic agents.

[0151] In some embodiments or aspects, the delivery system 100 can be configured to store, administer, and discard therapeutic or diagnostic agents, such as radiopharmaceutical therapeutics or diagnostic agents. The radiopharmaceutical therapeutics or diagnostic agents that can be stored and injected into the patient can be substances in a fluid. The radiopharmaceuticals can emit primarily alpha radiation or primarily beta radiation. In some embodiments or aspects, the radiopharmaceuticals can emit primarily Auger or positron radiation, and thus secondary gamma radiation. For substances that may emit primarily beta radiation, the storage device 200 and delivery system 100 can be adapted to accommodate secondary X-ray radiation that may be emitted as a result of beta radiation shielding, as described herein. The delivery system 100 can be adapted to accommodate gamma radiation that is further emitted by the radiopharmaceutical. In some examples or aspects, the delivery system 100 can be configured for storage, administration, and disposal of XOFIGO® treatments as well as other TRT treatments that may utilize targeted alpha or targeted beta therapy. Delivery system 100 may also be configured to work with radioisotopes (e.g., radioisotopes with very short half-lives such as technetium-99 or copper-64 that can be used for imaging or other purposes) that may be produced at the treatment site for therapeutic or diagnostic services.

[0152] In some embodiments or aspects, the delivery system 100 can be configured to store, administer, and dispose of therapeutic or diagnostic agents that are radiopharmaceuticals, such as imaging radiopharmaceuticals. The imaging radiopharmaceuticals may be gamma-emission imaging radiopharmaceuticals in some embodiments or aspects. Gamma-emission imaging radiopharmaceuticals include, but are not limited to, 99mTc, 123I, 111In, 67Ga, and / or 186Re. In some embodiments or aspects, the imaging radiopharmaceuticals may be positron-emission imaging radiopharmaceuticals. Positron-emission imaging radiopharmaceuticals include, but are not limited to, 13N, 18F, 68Ga, 89Zr, 124I, 64Cu, 82Rb, and / or 86Y.

[0153] In some embodiments or aspects, the delivery system 100 can be configured to store, administer, and dispose of therapeutic or diagnostic agents that are radiopharmaceuticals, such as therapeutic radiopharmaceuticals. The therapeutic radiopharmaceuticals in some embodiments or aspects may be beta therapy radiopharmaceuticals. Beta therapy radiopharmaceuticals include, but are not limited to, lutetium-177, iodine-131, yttrium-90, copper-67, rhenium-188, and / or holmium-166. The therapeutic radiopharmaceuticals in some embodiments or aspects may be alpha therapy radiopharmaceuticals. Alpha therapy radiopharmaceuticals include, but are not limited to, radium-223, actinium-225, thorium-227, astatine-211, lead-212, and / or bismuth-213. The therapeutic radiopharmaceuticals in some embodiments or aspects may be Auger therapy radiopharmaceuticals. Auger therapeutic radiopharmaceuticals include, but are not limited to, terbium-161 and / or iodine-125. In some embodiments or aspects, the radiopharmaceutical is selected from the group consisting of 177Lu-oxodotreotide, 223Ra dichloride, 18F-fluciclovine, 123I-iofulpane, 68Ga-dotatate, 111In, 99mTc-tilmanocept, 99mTc-tetrofosmin, 18F-florbetaben, 99mTc, 90Y-ibritumomab tiuxetan, 18F-florbetapir, 153Sm-lexidronam EDTMP, 131I-iobenguane MIBG, 89Sr-chloride. In some embodiments or aspects, the radionuclide of the radiopharmaceutical configured for imaging or therapy is linked to FAP (fibroblast activation protein), PSMA (prostate specific membrane antigen), DOTA (dodecanetetraacetic acid and its chelating derivatives), HER2 (human epidermal growth factor receptor 2), GPC-3 (glypican-3 protein) or other mechanism of action with the radiopharmaceutical.

[0154] In some embodiments or aspects, the delivery system 100 can be configured to work with radioisotopes (e.g., radioisotopes with very short half-lives, such as technetium-99m, nitrogen-13, fluorine-18, gallium-68, or copper-64) that can be made at the treatment site for therapeutic or diagnostic services that can be used for imaging or other purposes. These types of radioisotopes tend to have very short half-lives, which requires the imaging provider to prepare the radioisotope at an on-site hot lab or central radiopharmaceutical pharmacy to effectively use for diagnostic services. For such applications, the provider may prepare the diagnostic service material on-site. The provider may then insert the material into a vial, place the vial into a storage device, and record and affix a label to the storage device indicating the date of creation, volume of fluid, concentration, and / or initial radioactivity. The storage device may have a unique device identifier that is used to record content information in a software system. The storage device can then be coupled to cassettes, injectors, and infusion sets as described herein to provide the patient with a determined dose before the patient undergoes imaging. Used material can also be stored in a similar manner for disposal, etc., as described herein.

[0155] Below is a detailed description of the various components of delivery system 100 and how such components enable utilization of delivery system 100 for improved delivery, administration, and disposal of therapeutic or diagnostic agents.

[0156] With continued reference to FIG. 5, a delivery system 100 according to one embodiment or aspect of the present disclosure is shown. The delivery system 100 may be configured as a mobile device. The delivery system 100 includes a cart 102 supported on wheels 104 for moving the cart 102. In some embodiments or aspects, the delivery system 100 may be stationary mounted. The cart 102 includes multiple storage components 106, such as shelves or drawers, for storing various components of the delivery system 100. In some embodiments or aspects, the storage components 106 include a first drawer or shelf 108 for storing one or more storage devices 200 prior to use. The first drawer 108 may include the ability to keep the storage containers 200 at a low temperature to meet the requirements of the stored medication. The first drawer or shelf 108 may be further configured to store an infusion set and other fluid path components for connecting the delivery system 100 to a patient during administration of a therapeutic or diagnostic agent. The storage component 106 may include a second drawer or shelf 110 configured to receive components of the delivery system 100 for administering a therapeutic or diagnostic agent. For example, the second drawer or shelf 110 may be configured to receive one or more assemblies 150 for administering a dose of a therapeutic or diagnostic agent. As described herein, each assembly 150 includes a single storage device 200 connected to a single-use fluidic cassette 300. In some embodiments or aspects, the assembly 150 may include one or more multi-use storage devices 200 and multi-use fluidic cassettes 300. Each assembly 150 is removably insertable into the second drawer or shelf 110. The assembly 150 is operably connectable to an injector 170 for delivering a dose of a therapeutic or diagnostic agent. The assembly 150 may be configured for single use by a single patient. In some embodiments or aspects, the assembly 150 may be configured for use by multiple patients.

[0157] The delivery system 100 further includes a third drawer or shelf 112 configured to store one or more used assemblies 150. Each assembly is configured to minimize handling of the storage device 200 during workflow. At least one of the first, second, and third drawers or shelves 108, 110, 112 can have radiation shielding material to sufficiently reduce emissions or radioactivity outside of the cart 102.

[0158] With further reference to FIG. 5, the delivery system 100 further includes a controller 114 for controlling the delivery of doses of therapeutic or diagnostic agents. The controller 114 can be connected to one or more user displays 116 for displaying information regarding aspects of storage, administration, and / or disposal of the therapeutic or diagnostic agents. In some embodiments or aspects, the display 116 is a touch screen display that allows control by touch commands received from a user. The controller 114 can further be connected to an input device 118 for inputting data regarding storage, administration, and / or disposal of the therapeutic or diagnostic agents. In some embodiments or aspects, the input device 118 can be a barcode scanner, a keyboard, a mouse, a touch screen display, and / or any other input mechanism for inputting data and / or commands regarding the operation of the delivery system 100 to the controller 114. The input device 118 may include capabilities for video conferencing. The controller 114 can further be connected to a camera 117. The camera can be used to provide input to the controller, such as reading machine-readable or human-readable labels or tags. The camera may be used to take, record, and / or communicate images of everything that is going on for use by on-site operators, off-site operators, or for training or archival purposes. In some embodiments or aspects, an output device 119, such as a printer, is provided. The printer 119 may be used to print labels for documentation, labels to place on trash, ride cards for patients, reminders for patients, and / or guidelines for patients.

[0159] The controller 114 may include at least one processor programmed or configured to calculate a dose of a therapeutic or diagnostic agent to be delivered to a particular patient based on patient data and / or data regarding one or more characteristics of the therapeutic or diagnostic agent. The at least one processor of the controller 114 may be further configured to operate various components of the delivery system 100 to effect delivery of a dose to the patient according to a programmed protocol for the injection procedure. The controller 114 may include a computer-readable medium, such as a memory, in which one or more injection protocols may be stored for execution by the at least one processor.

[0160] The controller 114 of the delivery system 100 can be adapted to determine a dose of the therapeutic or diagnostic agent to be provided to the patient. The dose can be determined from one or more variables that can be provided to the controller 114 via one or more input devices 118. For example, the patient's weight or other patient characteristics can be input via a keyboard and / or mouse. The range of radiopharmaceutical activity of the therapeutic or diagnostic agent can be determined by the controller 114 based on information associated with a label or tag 270, such as a machine-readable label (e.g., barcode) or electronic tag (e.g., RFID) attached to the storage device 200 shown in FIG. 16. In some embodiments or aspects, the information associated with the label or tag 270 can include manufacturing information and / or radioactivity information (e.g., date of manufacture, date and time of calibration, radioactivity at time of calibration, radioactivity level of the material at time of manufacture, volume of fluid, concentration of fluid, type of radioisotope, etc.). In further embodiments or aspects, the information associated with the label or tag 270 can include time and temperature history values ​​of the storage device 200 during shipping and handling. This information, as well as the current date and time, can be used by the controller 114 to determine an appropriate dose for the patient through the use of predefined dosing algorithms that can utilize such parameters. Some predefined dosing algorithms can also use additional parameters, such as patient weight, patient gender, and / or patient age. Some predefined dosing algorithms can also use additional parameters, such as prescribed dose and prescribed or target tissue dose.

[0161] In some embodiments or aspects, the controller 114 can have different dosing algorithms for different predefined treatments and can utilize scanned bar codes, read RFID tags, and / or other inputs provided by a user to select the appropriate dosing algorithm to be executed to determine the patient's dose.

[0162] 5, each of the storage compartments 106 is lockable and configured to be accessed by an authorized user having an appropriate access protocol. For example, each of the storage compartments 106 may have a lock 120 operably connected to the controller 114. Operation of the lock 120 may require entry of a password or other authentication means, for example, using the display 116 and / or input device 118, to authenticate an authorized user of the delivery system 100.

[0163] With continued reference to FIG. 5 , one or more of the wheels 104 of the cart 102 may have a wheel lock 122 for selectively locking the wheels 104 to prevent movement of the cart 102. The wheel lock 122 may be configured to prevent unauthorized movement of the cart 102. For example, the wheel lock 122 may be operatively connected to the controller 114. Operation of the wheel lock 122 may require entry of a password or other authentication means, for example, using the display 116 and / or the input device 118, to authenticate an authorized user of the delivery system 100 and allow movement of the wheels 104. The wheel lock 122 may be a mechanical lock having a key or other mechanical locking mechanism. In some embodiments or aspects, the wheel lock 122 may be operatively connected to the lock 120 of the storage compartment 106 such that operation of one of the wheel lock 122 and the lock 120 also controls operation of the other of the wheel lock 122 and the lock 120. In some embodiments or aspects, an alarm system may be operatively connected to at least one of the lock 120 and the wheel lock 122 such that an alarm is sounded or an alarm message is provided for unauthorized use of the delivery system 100. In some embodiments or aspects, the alarm system may be configured to prevent operation of the delivery system 100 and / or movement of the cart 102, such as by locking the wheel lock 122. The cart 102 may also include a compartment 113 for storing auxiliary equipment that is not directly used in the injection process, but is necessary or useful throughout the procedure. For example, the cart 102 may house a survey meter or other radiation detector for inspecting the exterior of the packaging and / or storage container 200 when checking into the cart. The survey meter may also be used to inspect the exterior of the assembly 150 after injection to check for leaks. The survey meter may also be used to inspect the patient, the operator, and the injection room for contamination. The auxiliary equipment compartment 113 may also house a spill repair kit for the unusual case where a spill occurs, for example, if the IV exits the patient's arm during injection.The auxiliary equipment compartment may contain other items commonly found in hot labs and necessary for this infusion, as the advantage of this delivery system 100 is that it provides the capabilities and equipment necessary to safely deliver the drugs it is designed to deliver.

[0164] Referring to Figure 6, a delivery system 100' according to another embodiment or aspect of the present disclosure is shown. Similar to the delivery system 100 shown and described with reference to Figure 5, the delivery system 100' shown in Figure 6 is configured as a mobile device including a cart 102' supported on optional wheels. The cart 102' includes multiple storage components 106' for storing one or more storage devices 200 prior to use and for storing one or more used assemblies 150.

[0165] Instead of incorporating the injector 170 into the cart 102, the delivery system 100' shown in FIG. 6 has a separate injector 170' supported on a separate movable base 124. The injector 170' is configured to receive the assembly 150 including the storage device 200 and the fluid cassette 300. The delivery system 100' further includes a controller 114' for controlling the delivery of doses of therapeutic or diagnostic agents. The controller 114' can be connected to one or more user displays 116' for displaying information regarding aspects of the storage, administration, and / or disposal of the therapeutic or diagnostic agents. In some embodiments or aspects, the displays 116' are touch screen displays that allow control by touch commands received from a user. The user displays 116' can be configured to input data regarding the storage, administration, and / or disposal of the therapeutic or diagnostic agents. In some aspects, some of the communications may be wireless such that continuous physical connections are not required between selected components. In some embodiments of the system 100, there may be one or more fixed carts 102' and one or more mobile carts 102 that communicate with each other to facilitate flexible or optimal storage and use of the materials involved. In busy sites, used assemblies 150 may be transferred from the mobile carts to the fixed carts, which may provide secondary disintegration storage. This may be done, for example, by moving individual units or by transferring entire drawers from one cabinet to another at the end of the day. The secondary disintegration cabinets may be in different rooms or different facilities.

[0166] 7-9, a storage device 200 according to one embodiment or aspect of the present disclosure is shown. As described herein, the storage device 200 is configured to store a quantity of a therapeutic or diagnostic agent. In embodiments or aspects where the therapeutic or diagnostic agent is a radiopharmaceutical, the storage device 200 is configured to contain radiation emitted by a radioisotope of the radiopharmaceutical.

[0167] 8, the storage device 200 includes a housing 201 having a chamber 202 defined therein. The housing 201 has a body 204 defining the chamber 202. The body 204 has a proximal end 206 having a first opening 208 and a distal end 210 having a second opening 212. The distal end 210 of the body 204 of the housing 201 is provided with a cap 214 surrounding the second opening 212. In some embodiments or aspects, a gasket or seal 217 is provided at the interface between the cap 214 and the distal end 210 of the body 204. In some embodiments or aspects, the cap 214 is non-removably connected to the body 204 via, for example, one or more clips 216 (shown in FIG. 9). In some embodiments or aspects, the cap 214 may be removably connectable to the body 204. In some embodiments or aspects, the body 204 and cap 214 of the housing 201 may be made from, incorporate or contain a shielding material, such as poly(methyl methacrylate) (PMMA), lead, or tungsten.

[0168] 9, the body 204 has an inner portion 218 that defines a chamber 202 and an outer portion 220. The inner portion 218 may be connected to the outer portion 220 by one or more connectors 222. In some embodiments or aspects, a cavity 224 is defined between the inner portion 218 and the outer portion 220. The cavity 224 may be an air cavity or may be filled with one or more of a shielding material, such as PMMA, lead, or tungsten, a shock absorbing material, such as polystyrene beads, or an absorbent material, such as paper. The filling material may be formed from one or more of a solid sheet in a loose form, such as in the form of beads or pellets, a liquid, or a hardening injectable filler, or a combination thereof. The inner portion 218 and the outer portion 220 may have the same shape or different shapes. For example, the inner portion 218 may have a generally cylindrical shape and the outer portion 220 may have a generally rectangular parallelepiped shape. The edges of the cuboid shaped outer portion 220 may be rounded. In some embodiments or aspects, the inner portion 218 and the outer portion 220 may be monolithically formed.

[0169] For drugs that emit beta rays, the internal structure of the storage device 200 can be designed and configured to prevent x-rays formed from beta rays from emitting from the housing 201. This blocking of beta and x-rays can be affected by the inner structure of the storage device 200, such as a shielding material disposed within the cavity 224. Alternatively or in addition, the sidewalls of the housing 201 can also be selected, such as by selecting thickness and material properties, to prevent the emission of x-rays and beta rays. In some embodiments or aspects, the storage device 200 can have a plurality of spaced-apart shields (e.g., spaced-apart shield walls) defined between the chamber 202 and the outer wall of the housing 201. In some configurations, packing or fluid (e.g., air) can be disposed within the cavity 224 to provide sufficient shielding from x-rays and / or beta rays.

[0170] Alpha radiation is usually not difficult to block because alpha particles are large, have more limited penetrating power, and are generally administered at lower doses than beta. The side walls of the housing 201 can be selected to be of sufficient thickness to shield alpha radiation. Since many alpha and beta emitting isotopes or their daughter isotopes also emit gamma radiation, additional wall thickness or packing can be provided within the cavity 224 to help secure the container 226 in a desired position and / or provide additional shielding to prevent additional radiation exposure from the radiopharmaceutical from emitting from the housing. The size of the housing 201 relative to the container 226 can be selected to set a minimum distance from the exterior of the housing 201 to the container 226 to reduce user exposure. However, isotopes generally emit multiple types of radiation or radiation at different energy levels with different penetrating powers. In addition, all isotopes have some accumulation of daughter products during the manufacture and delivery of the drug. Thus, significant gamma shielding may be required for what are nominally alpha or beta emitters. The materials used in shielding and the guidelines involved are well known to those in the health physics field.

[0171] 8-9, chamber 202 of housing 201 is configured to hold container 226 (shown in FIG. 8) that houses therapeutic or diagnostic agent 228 therein. Container 226 may be a glass vial that is formed separately from housing 201 of storage device 200 and inserted into chamber 202 of housing 201. In some embodiments or aspects, container 226 may be formed integrally with storage device 200. The size of chamber 202 is selected to accommodate the largest container 226 that may be used with storage device 200 and / or to account for any additional packing or shielding materials that may be required.

[0172] The container 226 has a proximal end 230 with an access port 232 and a closed distal end 234 defining an interior 236 between the proximal end 230 and the distal end 234. The access port 232 may be a pierceable septum configured to be pierced by a container access member or other access mechanism to access the therapeutic or diagnostic agent 228 within the interior 236 of the container 226, as described herein. During manufacture of the therapeutic or diagnostic agent 228, the agent 228 can be filled into the container 226, and the container 226 can then be sealed via the access port 232 to retain the agent 228 therein. Filling of the container 226 can occur after the container 226 is connected or placed within the chamber 202 of the storage device 200, or prior to connecting or placing the container 226 within the chamber 202. In some embodiments or aspects, the access port 232 can be fully sterilized at the point of manufacture. The container 226 may also be a plastic vial, flexible bladder, collapsible bag, or pre-filled syringe, preferably having a plunger but no handle to reduce the space required. The advantage of collapsible containers and pre-filled syringes is that there is no need to fill the container with air when fluid is removed because the container collapses or the plunger moves downward as the fluid is drawn.

[0173] 8, the proximal end 230 of the container 226 is disposed at the proximal end 206 of the housing 201 such that the access port 232 is disposed opposite the first opening 208. In this manner, the container access member can extend through the first opening 208 of the housing 201 and through the access port 232 of the container 226 during administration of the therapeutic or diagnostic agent 228.

[0174] In some embodiments or aspects, the container 226 may be secured to the proximal end 206 of the housing 201 by a plurality of ribs 238 that surround the first opening 208 in the chamber 202 of the housing 201. Each of the plurality of ribs 238 may be configured to engage the proximal end 230 of the container 226 to secure the position of the access port 232 relative to the first opening 208 of the housing 201.

[0175] 8-9, the storage device 200 has a holder 240 in the chamber 202 of the housing 201. The holder 240 can be configured to hold the distal end 234 of the container 226 relative to the housing 201. The holder 240 can contact the distal end 234 of the container 226 to fix the position of the container 226 relative to the housing 201. In some embodiments or aspects, the holder 240 includes a contact element 242 for contacting the distal end 234 of the container 226 and a plurality of tabs 244 connected to the contact element 242 and configured to engage the housing 201, such as the inner surface 246 of the inner portion 218 of the housing 201, to fix the position of the container 226 relative to the housing 201. As shown in FIGS. 9-10, the plurality of tabs 244 can be angled relative to the contact element 242 such that they are oriented at a non-perpendicular angle relative to the inner surface 246 of the inner portion 218 of the housing 201. The plurality of tabs 244 may flex relative to the contact element 242 such that when the contact element 242 is pressed against the distal end 234 of the container 226, the plurality of tabs 244 provide a restoring force against movement of the holder 240 in a distal direction, away from the distal end 234 of the container 226. In this manner, the holder 240 is configured to hold a plurality of different containers 226, regardless of their diameters and longitudinal lengths.

[0176] 8-9, the storage device 200 has a door 248 associated with the housing 201. In some embodiments or aspects, the door 248 may be movable relative to the housing 201 between a closed position, shown in FIG. 8, and an open position. The door 248 may be movable between the closed position and the open position in response to actuation by an access mechanism of the delivery system 100, as described herein. In some embodiments or aspects, the door 248 may be normally closed. In the closed position, the door 248 is configured to cover the first opening 208 of the housing 201 and enclose the chamber 202 of the housing 201. In this manner, the container 226 is fully enclosed within the chamber 202, preventing access to the access port 232. In the open position, the door 248 is moved relative to the housing 201 to expose the first opening 208 in the housing 201 for accessing the access port 232 of the container 226. In some embodiments or aspects, the door 248 may be slidably moveable relative to the housing in the direction of arrow A shown in FIG.

[0177] 8-9, the door 248 has an access opening 250 configured to align with the first opening 208 of the housing 201 when the door 248 is in the open position. In this manner, the container access member can extend through the access opening 250 and the first opening 208 and into the access port 232 of the container 226.

[0178] 8-9, a door cover 252 is connected to the housing 201 and configured to enclose the door 248 within the door chamber. The door cover 252 is non-removably connected to the body 204, for example, via one or more clips 216 (shown in FIG. 9). In some embodiments or aspects, the door cover 252 may be removably connectable to the body 204 of the housing 201. In some embodiments or aspects, the door cover 252 may be made of the same material as the body 204 and the cap 214 of the housing 201.

[0179] 9, door cover 252 has a door access opening 254 with a seal 256 and a container access opening 258 (shown in FIG. 8) disposed opposite first opening 208 of housing 201. Container access opening 258 is configured to receive a spike or other container access member of a delivery system during administration of therapeutic or diagnostic agent 228. Container access opening 258 aligns with access opening 250 on door 248 when door 248 is in the open position to allow the spike or other container access member to extend through first opening 208 of housing 201 to access access port 232.

[0180] 12, the seal 256 covers the door access opening 254 and is penetrable by the access mechanism of the delivery system 100 as described herein. In some embodiments or aspects, the access mechanism of the delivery system 100 may be configured to sense the presence of the seal 256, such as by sensing resistance to movement through the door access opening 254 when the seal 256 is present. If the access mechanism of the delivery system 100 does not detect the seal 256, such as because there is no resistance to movement through the door access opening 254, the controller 114 may be configured to prevent operation of the delivery system 100 because a used storage device 200 (i.e., one in which the seal 256 has been penetrated) or a tampered storage device 200 (i.e., one in which the seal 256 has been removed) has been installed for use with the delivery system 100. In this manner, the seal 256 functions as a security mechanism to ensure that only an untampered storage device 200 can be used with the delivery system 100. In some embodiments or aspects, the seal 256 may also be provided over the container access opening 258. In some embodiments, the seal may be a member of the housing 201 that breaks off or is permanently deformed as evidence of use or tampering.

[0181] 13-14, a door lock 260 according to some embodiments or aspects is shown. The door lock 260 may be provided on the door 248 to lock the door 248 in an open position after the door 248 is moved from a closed position to an open position. In some embodiments or aspects, the door lock 260 includes at least one first hook 262 configured to engage with at least one second hook 264 on the housing 201 or on the door cover 252 (shown in FIGS. 8-9). Each of the at least one first hook 262 and the at least one second hook 264 may have an inclined contact surface 266 and a catch 268 configured to engage after the two contact surfaces 266 slide past each other. FIG. 14 shows the at least one first hook 262 and the at least one second hook 264 in a locking engagement with each other when the door 248 is in an open position. This locking engagement prevents the door 248 from being returned to the closed position.

[0182] In some embodiments or aspects, the door 248 may be movable between three different positions. In the initial position, the door 248 may be closed. In the intermediate position, the door 248 may be moved from the initial (closed) position to an open position to allow access to the container 226. In the final position, the door 248 may be moved to a closed position where the door 248 is engaged with the door lock 260 to prevent the door 248 from being opened again to access the remaining contents within the container 226.

[0183] Referring to Figures 15-19, a storage device 200' according to another embodiment or aspect of the present disclosure is shown. The structure of the storage device 200' shown in Figures 15-19 is substantially similar to the structure of the storage device 200 shown and described with reference to Figures 7-14, so a detailed description of the components of the storage device 200' will be omitted. In Figures 15-19, the same reference numbers used in Figures 7-14 to describe the components of the storage device 200 are used to describe the components of the storage device 200, except that a "'" mark is added after each reference number in Figures 15-19. The following detailed disclosure will focus only on the relative differences between the two storage devices.

[0184] In some embodiments or aspects, the storage device 200 may have at least one label, tag, or other indicia 270 on the housing 201. Although the at least one label, tag, or other indicia 270 is illustrated with respect to the embodiment of the storage device shown in FIG. 16, the at least one label, tag, or other indicia 270 may be applied to any storage device 200 described herein, such as the storage devices 200 described herein with reference to FIGS. 7-14. The at least one label, tag, or other indicia 270 may include machine-readable authenticable data configured to be read by the delivery system 100 to authenticate the storage device 200 prior to use. In some embodiments or aspects, the machine-readable authenticable data includes at least one of product information, production information, prescription information, and shipping terms information. At least one label, tag, or other indicia 270 may be a label (e.g., a bar code, QR code, or the like) and / or tag (e.g., electronic, RFID, or the like) that includes at least one of product, production, prescription, and shipping terms information regarding the therapeutic or diagnostic agent. In some embodiments or aspects, at least one label, tag, or other indicia 270 may include a data logger configured to record, for example, temperature, shock, and / or pressure data. In some embodiments or aspects, at least one label, tag, or other indicia 270 may include a link to access information from a website or database.

[0185] In some embodiments or aspects, the storage device 200' can be configured such that the storage device 200' can only be connected to a fluidic cassette in a particular orientation. In this manner, the access opening 254' on the door cover 252' of the storage device 200' can be properly aligned with the fluidic cassette for proper connection of the container access member with the access port 232' on the container 226'. With reference to FIGS. 15-17B, the housing 201' of the storage device 200' includes a guide mechanism 272 configured to position the storage device 200' in a desired orientation relative to the fluidic cassette 300 (see, e.g., FIG. 28). In some embodiments or aspects, the guide mechanism 272 includes one or more geometric features, such as grooves, chamfers, protrusions, holes, or tabs, that can be configured to mate with corresponding features of the fluidic cassette 300 to provide a direct connection to the fluidic cassette 300 in a predetermined orientation.

[0186] 17A-17B, the storage device 200' may have at least one identification feature 274 (shown in FIG. 17B) that may be used to identify a particular characteristic of the storage device 200', such as the type of therapeutic or diagnostic agent in the storage device 200'. The at least one identification feature 274 may be one or more geometric features or physical indicia, such as grooves, chamfers, protrusions, holes or tabs. Such geometric features may be used to identify a particular storage device 200' and / or verify that the storage device 200' is an authentic storage device 200'. The at least one identification feature 274 may have a corresponding identification feature on the fluidic cassette 300. The same or different identification feature 274 may be used in connection with other aspects of the system, such as the storage compartment 108 and the used container compartment 112. This provides tangible feedback that the drug in the storage container 200' complies with the shielding and temperature capabilities of the applicable storage compartment.

[0187] In some embodiments or aspects, at least a portion of the housing 201' of the storage device 200' may have a colored portion that may be used for identification purposes. For example, a particular color of at least a portion of the housing 201' of the storage device 200' may be used to identify the contents of the storage device 200', such as the type of therapeutic or diagnostic agent contained therein. In some embodiments or aspects, a particular color of at least a portion of the housing 201' of the storage device 200' may be used to identify the storage device 200' as a storage device 200' intended for training purposes only. Such a storage device 200' does not contain any therapeutic or diagnostic agent other than a safe, non-hazardous liquid, optionally colored so that its behavior can be visualized.

[0188] 18-19, a storage device 200' includes a housing 201' having a chamber 202' (shown in FIG. 19) defined therein. The housing 201' has a body 204' having a proximal end 206' with a first opening 208' and a closed distal end 210'. Instead of having a cap 214 at the distal end 210, as shown in the storage device 200 of FIGS. 7-9, the storage device 200' shown in FIGS. 18-19 has a proximal cap 276 at the proximal end 206' of the housing 201' configured to surround the first opening 208'.

[0189] 18-19, the proximal cap 276 has a retainer 278 having a base 280 connectable to at least one of the body 204' and the door cover 252' and a retaining portion 282 projecting distally from the base 280. The retaining portion 282 has a generally cylindrical shape having an inner surface 284 configured to engage the container 226' and an outer surface 286 having a threaded collar 288. The threaded collar 288 is configured to threadably engage a cover 290 that surrounds the container 226' within the chamber 202'. The cover 290 has threads 292 configured to threadably engage the threaded collar 288 of the retaining portion 282. A distal end 294 of the cover 290 has an inner engagement surface 296 configured to contact the distal end 234' of the container 226'. A seal 298 may be provided at the interface between the retaining portion 282 and the cover 290.

[0190] Referring to FIG. 20, an assembly 150 having a storage device 200 and a fluidic cassette 300 is shown according to some embodiments or aspects of the present disclosure. As described herein, the assembly 150 is configured to deliver a therapeutic or diagnostic agent from the storage device 200 via the fluidic cassette 300 using an injector 170 (shown in FIG. 5). The fluidic cassette 300 is configured to be removably connectable to the injector 170 and can be connected to a saline source for saline flush applications, priming, saline test injections, and saline injections. The fluidic cassette 300 is further configured to connect to a container 226 (shown in FIG. 8) of the storage device 200 for delivery of a therapeutic or diagnostic agent 228 to a patient using the injector 170.

[0191] In some embodiments or aspects, the storage device 200 and the fluidic cassette 300 may be configured to be removably connectable to one another. In other embodiments or aspects, the storage device 200 and the fluidic cassette 300 may be configured to be non-removably connectable to one another such that the storage device 200 cannot be removed from the fluidic cassette 300 when the storage device 200 is connected to the fluidic cassette 300. This type of interlocking connection helps to prevent undesired contact with therapeutic or diagnostic agents. Each fluidic cassette 300 may be adapted to connect to one storage device 200 or a pair of storage devices 200. In further embodiments or aspects, the fluidic cassette 300 may only be fluidly connectable to the storage device 200 without a direct physical connection between their housings.

[0192] 21, the fluidic cassette 300 is shown without the storage device shown in FIG. The fluidic cassette 300 includes an enclosure 302 that encloses various components of the fluidic cassette 300. The enclosure 302 has a first portion 304 and a second portion 306. The first and second portions 304, 306 may be removably or non-removably connectable to one another. In some embodiments or aspects, the fluidic cassette 300 may have a generally rectangular parallelepiped shape.

[0193] 22, the first and second portions 304, 306 of the enclosure 302 of the fluidic cassette 300 define an interior 308 configured to receive components of the fluidic cassette 300. In some embodiments or aspects, the fluidic cassette 300 may have a container access member, such as a spike 310, a metering device, such as a syringe 312, and a fluidic pathway set 314 received within the interior 308 of the enclosure 302. The fluidic pathway set 314 has a tube fluidly connecting the spike 310 to the syringe 312. In some embodiments or aspects, the fluidic pathway set 314 may have a particle / air filter 317 (shown in FIG. 31). In further embodiments or aspects, the fluidic pathway set 314 may have a valve block, as described herein with reference to FIG. 31. In some embodiments, the valve block may have one or more valves for controlling the flow of fluid through the spike 310, the syringe 312, and the fluidic pathway set 314. The fluid pathway set 314 is further configured to connect to an infusion set, as described herein with reference to FIG.

[0194] 22, the spike 310 is configured to be extendable through the spike opening 315 of the enclosure 302 between a stored position and an extended position in the direction of arrow B. In the stored position, the spike 310 is contained within the interior 308 of the enclosure 302. In the extended position, the spike 310 protrudes from the interior 308 of the enclosure 302 through the spike opening 315 such that the spike 310 is insertable through the access port 232 (shown in FIG. 8) of the container 226. The spike opening 315 of the fluidic cassette 300 may be provided with an alignment element 337 for aligning the storage device 200 with respect to the fluidic cassette 300 such that the spike 310 is axially aligned for insertion into the access port 232 of the container 226 when the storage device 200 is connected to the fluidic cassette 300. A cap may be provided to surround the spike opening 315 prior to use of the fluidic cassette 300.

[0195] As shown in FIG. 23, the spike 310 has a body 320 having a proximal end 322, a distal end 324, and having a hollow interior. The distal end 324 of the spike 310 has at least one piercing tip 326 configured to pierce an access port 232 (shown in FIG. 8) of the container 226. The at least one piercing tip 326 may include two piercing tips 326, a first of the two piercing tips 326 configured to draw fluid from the container 226 and a second of the two piercing tips 326 configured to pump air into the container 226 as fluid is drawn from the container 226. The at least one piercing tip 326 is in fluid communication with the hollow interior of the body 320 of the spike 310 to deliver fluid from the access port 232 of the container 226 to a fluid pathway connector 328 adapted to connect to the fluid pathway set 314. In this manner, a therapeutic or diagnostic agent from the container 226 can be delivered to the fluid pathway set 314 via at least one piercing tip 326 and fluid pathway connector 328 of the spike 310. In some embodiments or aspects, the spike can have a filtered vent 329 configured to allow air to enter the container 226 as fluid is withdrawn from the container 226. The spike 310 can have a collar 330 extending around the body 320. In some embodiments or aspects, an absorbent material 332 can be provided on the collar 330 to absorb dripping from the access port 232 as the spike 310 is inserted into or withdrawn from the access port 232. The spike 310 further has a drive element 334 configured to engage with a spike drive of a delivery system, as described herein. The drive element 334 can be an opening, slot, or other mechanism configured to be engaged by a spike drive of a delivery system to move the spike 310 between a retracted position and an extended position. As shown in FIG. 22, spike drive slots 336 may be provided on the enclosure 302 to allow a spike drive of the delivery system to extend into the interior 308 of the enclosure 302 to engage the spikes 310.

[0196] 22, the syringe 312 has a barrel 338 having a proximal end 340 opposite a distal end 342 and an internal chamber 344 defined therebetween. The proximal end 340 is open and configured to receive a plunger 346. The distal end 342 has a port 350 in fluid communication with the fluid pathway set 314. The plunger 346 is reciprocable within the barrel 338 of the syringe 312 via a syringe drive of the delivery system, as described herein. The plunger 346 is movable in the direction of arrow C, with movement of the plunger 346 in a proximal direction drawing fluid into the internal chamber 344 via the port 350 and movement of the plunger 346 in a distal direction expelling fluid from the internal chamber 344 via the port 350. As shown in FIG. 21, a portion of the plunger 346 protrudes from the enclosure 302 through a plunger opening 352. In some embodiments or aspects, a syringe drive of the delivery system can be configured to engage a proximal end of the plunger 346 that protrudes through the plunger opening 352. In other embodiments or aspects, the plunger 346 can be completely contained within the housing 302 of the fluidic cassette 300.

[0197] 24, the barrel 338 of the syringe 312 has a flange 354 that projects radially outward from the barrel 338 at the distal end 342. The flange 354 is configured to be received in a flange slot 356 on the enclosure 302 to prevent movement of the barrel 338 relative to the enclosure 302 when the plunger 346 reciprocates within the barrel 338. The flange slot 356 may have a tapered shape to ensure a tight fit with the flange 354.

[0198] 25A-25B, the plunger 346 has a plunger cap 358 configured to lock the plunger 346 in a locked position and prevent movement of the plunger such that the filling and dispensing functions of the syringe 312 (shown in FIG. 22) are disabled. In some embodiments or aspects, the plunger cap 358 may be shipped in a locked configuration, and the injector 170 may be configured to unlock the plunger cap 358 to allow movement of the plunger 346 for the filling and dispensing functions. In some embodiments or aspects, the plunger cap 358 has at least one first hook 362 configured to engage with at least one second hook 364 on the enclosure 302. Each of the at least one first hook 362 and the at least one second hook 364 may have an angled contact surface 366 and a catch 368 configured to engage after the two contact surfaces 366 slide past each other. 25B illustrates at least one first hook 362 and at least one second hook 364 that lockingly engage with one another when the plunger cap 358 is biased towards the enclosure 302. This locking engagement prevents the plunger 346 from being moved to fill or dispense fluid from the syringe 312. The plunger cap 358 is further configured to maintain the position of the syringe 312 in a set position such that the plunger 346 can be connected to a plunger drive mechanism during installation of the fluid cassette 300 into the delivery device 100.

[0199] 26, the fluidic cassette 300 has one or more alignment elements 370 for aligning the fluidic cassette 300 relative to the injector 170 (shown in FIG. 5) of the delivery system 100. In some embodiments or aspects, the enclosure 302 of the fluidic cassette 300 has a pair of alignment elements 370 configured as openings shaped to receive alignment pins 176 (also shown in FIG. 31) of the injector 170. Each of the pins 176 has a tapered surface configured to position the alignment element 370 on the fluidic cassette 300 when the alignment pins 176 are moved in a direction toward the fluidic cassette 300. When the alignment pins 176 are inserted into the alignment elements 370, the fluidic cassette 300 is positioned in a desired position relative to the injector 170 to allow manipulation of the spike 310 and plunger 346. For example, alignment of alignment pin 176 with alignment element 370 on fluidic cassette 300 also aligns delivery mechanism 174 with a corresponding plunger drive receiver 376 on plunger cap 358 to move plunger 346 during fill and dispense operations. Plunger drive receiver 376 may have a tapered shape that corresponds to the tapered shape of the pin on delivery mechanism 174. In some embodiments or aspects, alignment element 370 further facilitates alignment of valves and sensors of delivery device 100 with corresponding locations on fluid pathway set 314 in fluidic cassette 300.

[0200] 27-30, a fluidic cassette 300' according to another embodiment or aspect of the present disclosure is shown. The structure of the fluidic cassette 300' shown in FIGS. 27-30 is substantially similar to the structure of the fluidic cassette 300 shown and described with reference to FIGS. 20-26, and therefore a detailed description of the components of the fluidic cassette 300' will be omitted. In FIGS. 27-30, the same reference numbers used in FIGS. 20-26 to describe the components of the fluidic cassette 300 are used to describe the components of the fluidic cassette 300, except that a "'" mark is added after each reference number in FIGS. 27-30. The following detailed disclosure will focus only on the relative differences between the two storage devices.

[0201] 27, the fluidic cassette 300' has an enclosure 302' having a recess 378 shaped to receive the storage device 200' shown in FIGS. 15-19. In some embodiments or aspects, the recess 378 is shaped so that the storage device 200' can be connected to the fluidic cassette 300', and the resulting assembly 150 has a generally rectangular parallelepiped shape. As described herein with reference to FIGS. 15-17B, the housing 201' of the storage device 200' includes a guide feature 272 configured to position the storage device 200' in a desired orientation relative to the fluidic cassette 300'. For example, with reference to FIG. 28, the guide feature 272 includes one or more geometric features, such as a groove, chamfer, protrusion, hole, or tab, that can be configured to mate with a corresponding guide feature 380 of the fluidic cassette 300' to provide for direct connection of the storage device 200' to the fluidic cassette 300' in a predetermined orientation. With reference to FIG. 29, the fluidic cassette 300' has one or more locking elements 382 for non-removably connecting the storage device 200' to the fluidic cassette 300'.

[0202] 31, an exemplary fluid diagram illustrating the fluid paths between the storage device 200 and the fluid cassette 300 is shown. As shown in FIG. 31, the container 226 of the storage device 200 is fluidly connectable to the fluid path set 314 of the fluid cassette 300 via the spike 310. The fluid path set 314 may have multiple valves for controlling the flow of fluid from the container 226 to the infusion set 406. In some embodiments or aspects, a first valve 384 is provided downstream of the spike 310 to regulate the inflow of fluid from the spike 310 to the fluid path set 314. In some embodiments or aspects, the first valve 384 may be a pinch valve, a stopcock valve, or any other type of valve configured to selectively allow the flow of fluid from the spike 310 to the fluid path set 314. In some embodiments or aspects, the first valve 384 may be operable between an open position and a closed position by the injector 170.

[0203] The flow paths of the fluid path set 314 can be constructed to facilitate air removal during priming and limit the formation of air bubbles in the material passing from the container 226 of the storage device 200 to the syringe 312, for example, by limiting abrupt changes or transitions in the inner diameter of the tubing of the fluid path set 314. The flow paths of the fluid path set 314 can be further constructed to prevent any air bubbles from passing from the syringe 312, incorporating a tortuous fluid path to preferentially separate and bypass air bubbles or with a hydrophobic membrane. The flow paths of the fluid path set 314 can be designed to incorporate valves or other fluid control elements, such as passive valves, active valves, one-way valves, selector valves, pinch valves, rotary valves, stopcocks, or on-off valves.

[0204] 31, an air detector 180 is provided downstream of the first valve 384. The air detector 180 is configured to detect air in the fluid path set 314. In some embodiments or aspects, the air detector 180 is provided on the injector 170 (see FIGS. 5 and 32) and the fluid cassette 300 is positioned relative to the injector 170 such that the air detector 180 is configured to detect air in the fluid path set 314 at a location downstream of the first valve 384. In some embodiments or aspects, an output from the air detector 180 can be used by the controller 114 of the delivery system 100 (shown in FIG. 5) to allow or prevent operation of the injector 170 depending on the absence or presence of air in the fluid path set 314. The air detector 180 may be configured to detect the presence of a therapeutic or diagnostic agent in the line from the container 226 to assist with volumetric accuracy of dose delivery.

[0205] 31, an air / particle filter 317 is provided downstream of the air detector 180. In some embodiments or aspects, a valve block 316 is provided downstream of the air detector 180. In some embodiments or aspects, the valve block 316 may be a manifold having a number of ports that can be selectively opened and closed to allow or restrict fluid flow therethrough. For example, the valve block 316 may have a first port 388, a second port 390, and a third port 392. The valve block 316 is operable such that only two of the three ports can be in fluid communication with each other. For example, when the valve block 316 is positioned such that the first and second ports 388, 390 are in fluid communication with each other and are fluidly isolated from the third port 392, the syringe 312 can be filled with a therapeutic or diagnostic agent from the container 226 via the port 350. When the valve block 316 is positioned such that the second and third ports 390, 392 are in fluid communication with one another and fluidly isolated from the first port 388, fluid from an auxiliary fluid source 394, such as a saline source, can be delivered to the port 350 of the syringe 312 via the auxiliary line 396. In this configuration, saline or other fluids can be delivered for patency checks, test injections, or flushing procedures, as described herein. The auxiliary line 396 is connectable to an auxiliary branch 398 of the fluid path set 314. The auxiliary line 396 has a spike 395 for connecting to the auxiliary fluid source 394, a check valve 397, and a pair of connectors 399.

[0206] In some embodiments, a second valve 400 may be provided in the auxiliary branch 398 to control the flow of fluid to the valve block 316. In some embodiments or aspects, the valve block 316 may be operable to selectively open and close the first, second, and third ports 388, 390, 392 via the injector 170. Similarly, the second valve 400 may be operable between open and closed positions via the injector 170.

[0207] 31 , a third valve 402 is provided downstream of the port 350 of the syringe 312. The third valve 402 may be operable between an open position and a closed position via the injector 170. An air / particulate filter 403 is provided downstream of the third valve 402 before the fluid path set 314 terminates in an end connector 404.

[0208] 31 , the infusion set 406 is removably connectable to the fluid pathway set 314 of the fluid cassette 300 via the end connector 404. The infusion set 406 has a proximal connector 408 configured to removably connect with the end connector 404 of the fluid pathway set 314. In some embodiments or aspects, the end connector 404 and the proximal connector 408 may be luer connectors. The infusion set 406 further has a distal connector 410 configured to connect to the catheter 412 or the priming cap 414. A pair of check valves 416 are provided between the proximal connector 408 and the distal connector 410. In some embodiments or aspects, the infusion set 406 may be configured to connect to a sensor device 416 having an occlusion detection sensor 418 and an air detector 420. In some embodiments or aspects, the occlusion detection sensor 418 may be configured to pressure test the integrity of the fluid pathway set 314 before accessing the container 226.

[0209] 32, the fluid cassette 300 and storage device 200 are shown along with components of an injector 170 configured to interact with the fluid cassette 300 and storage device 200. In some embodiments or aspects, the injector 170 includes an access mechanism 172 configured to move a door 248 (shown in FIG. 8) of the storage device 200 from a closed position to an open position. The injector 170 further includes a delivery mechanism 174 configured to actuate a plunger 346 of the syringe 312 to fill the syringe 312 with a therapeutic or diagnostic agent from the storage device 200 or to fill the syringe 312 with saline from an auxiliary fluid source 394 (shown in FIG. 31). The delivery mechanism 174 may be further configured to actuate the plunger 346 of the syringe 312 to deliver the contents of the syringe 312, such as the therapeutic or diagnostic agent, or saline, to an infusion set 406 (shown in FIG. 31). Although the fluid cassette 300 and its fluid path elements are shown with a single syringe 312 and valving to move and control the fluids, pumps other than a single syringe 312 may be used. In some embodiments or aspects, there may be multiple pumps, e.g., one syringe 312 each for the drug and the flushing fluid. In some embodiments, one or more of the pumps may be peristaltic, diaphragm, or piston pumps. In some embodiments, the additional pumps may eliminate some valves or may benefit from the use of additional valves. In some embodiments, it is desirable to have separate pumps for the drug and the flushing fluid from the auxiliary fluid source 394 to provide the ability to have a dual flow, i.e., to deliver two fluids simultaneously, so that the total volumetric flow rate may be set independently of the drug delivery rate. One advantage of the dilution introduction is that it likely reduces the possibility of patient discomfort or reaction. The second is that it reduces the time that the TRT is in the infusion vein before it is introduced into the central circulation and diluted. See, for example, U.S. Patent Application Publication No. 2021 / 0187186, which is incorporated by reference herein.

[0210] 32, the fluid injector has one or more alignment pins 176 configured to engage one or more alignment elements 370 on the fluid cassette 300. When the alignment pins 176 are inserted into the alignment elements 370, the fluid cassette 300 is positioned in a desired position relative to the injector 170 to allow manipulation of the spike 310 and plunger 346. The injector 170 further has an air detector 180 configured to detect air in the tubing of the fluid path set 314. In some embodiments or aspects, the injector 170 may further have a fluid detector configured to detect the presence of fluid and / or other characteristics related to the fluid. In some embodiments or aspects, the injector 170 further has a valve assembly 178 configured to selectively engage the tubing of the fluid path set 314 to regulate the flow of fluid therethrough.

[0211] When the storage device 200 is coupled to the fluid cassette 300 and the combined assembly 150 is installed in the delivery system 100, the access mechanism 172 of the injector 170 is configured to move the door 248 from a closed position to an open position so that the spike 310 of the fluid cassette 300 can extend to penetrate the access port 232 of the container 226. With reference to FIG. 33, the access mechanism 172 of the injector 170 can have a probe 182 configured to extend in a direction toward the door 248 through the access opening 254 of the door cover 252 (shown in FIG. 9). In some embodiments or aspects, the probe 182 can be configured to penetrate the seal 256 on the access opening 254. The probe 182 can be configured to sense the presence of the seal 256, for example, by sensing resistance to movement through the door access opening 254 when the seal 256 is present compared to resistance to movement when the seal 256 is not present. If the probe 182 does not detect the seal 256, such as because there is no resistance to movement through the door access opening 254, the controller 114 (shown in FIG. 5 ) may be configured to prevent operation of the delivery system 100 because a used storage device 200 (i.e., one with the seal 256 pierced) or a tampered storage device 200 (i.e., one with the seal 256 removed) has been placed in the fluid. Operation of the probe 182 may be controlled via the controller 114.

[0212] 33, the access mechanism 172 of the fluid infuser may further include a spike driver 184 configured to engage with a spike drive slot 336 (shown in FIG. 23) of the spike 310. The spike driver 184 may be linearly movable from a first position corresponding to a retracted state of the spike 310 and a second position corresponding to an extended state of the spike 310 in which the spike 310 penetrates the access port 232 of the container 226. Operation of the spike driver 184 may be controlled via the controller 114.

[0213] 33, the delivery mechanism 174 includes a plunger driver 186 configured to actuate the plunger 346 of the syringe 312 to move the plunger 346 within the barrel of the syringe 312. The plunger driver 186 is shaped to be received in the plunger drive receiver 376 such that movement of the plunger driver 186 causes a corresponding movement of the plunger 346. The plunger driver 186 may have a motor for moving the plunger 346 in a linear direction. The plunger driver 186 may be linearly movable in a first direction configured to cause the barrel of the syringe 312 to fill with fluid and a second direction opposite the first direction configured to cause fluid from the barrel of the syringe 312 to be delivered through the port 350. The operation of the plunger driver 186 may be controlled via the controller 114. In some embodiments or aspects, the plunger driver 186 determines the flow rate of fluid delivered to the patient.

[0214] 33, air detector 180 is configured to detect air within the tubes of fluid path set 314. Air detector 180 may be an optical air detector, an acoustic air detector, an ultrasonic air detector, or any other air detector configured to detect the presence of air within the tubes of fluid path set 314. The operation of air detector 180 may be controlled via controller 114.

[0215] 33, the valve assembly 178 may include a plurality of valves 188. In some embodiments or aspects, the plurality of valves 188 may be pinch valves configured to pinch tubing of the fluid pathway set 314. In some embodiments or aspects, the valves 188 may be rotary stopcocks or other fluid flow shutoff mechanisms. Operation of the valve assembly 178 may be controlled via the controller 114.

[0216] With reference to FIG. 34, a sterilization mechanism 190 is provided for sterilizing the access port 232 of the container 226. In some embodiments or aspects, the sterilization mechanism 190 includes a movable arm 192 and a sterilization source 194. The movable arm 192 is movable relative to the storage device 200 such that the sterilization source 194 can be positioned on an opposite side of the access port 232. The sterilization source 194 can include, for example, a laser or light emitter capable of emitting electromagnetic energy at a wavelength capable of inactivating organisms on the surface of the access port 232. Examples of such electromagnetic energy that can be emitted include, for example, ultraviolet (UV) light (10-400 nanometer (nm) wavelength light), ultraviolet C (UV-C) light (light having a wavelength of 200-280 nm), white light, infrared (IR) light, laser, etc. (e.g., the sterilization mechanism can include a UV light emitter, a UVC LED, an IR emitter, etc.). The emitted light can be emitted continuously onto the surface of the access port 232 for a preselected disinfection period to deliver a sufficient amount of energy to inactivate organisms on the access port 232 before the spike 310 is inserted through the access port 232 into the container 226. In some embodiments or aspects, the disinfectant source 194 can be configured to disinfect the access port 232 and the spike 310 of the container 226. In this manner, the access port 232 and the spike 310 are disinfected for a sterile connection therebetween. In further embodiments or aspects, a second disinfectant source 194 can be provided on the movable arm 192 to disinfect the spike 310 before inserting the spike 310 into the access port 232 of the container 226.

[0217] In some embodiments or aspects, the sanitizing source 194 may include a nozzle or sprayer that can spray a sanitizing substance onto the access port, and / or an agitation mechanism that can scrub the sanitizing agent onto the access port for a preselected sanitizing period. The sanitizing period selected may be based on the type of sanitizing agent utilized and the period of time required to eliminate a preselected set of organisms with the sanitizing agent or reduce the amount of such organisms below a preselected threshold level. In some embodiments or aspects, the sanitizing agent may be applied at the manufacturing site via a sanitizing agent-containing absorbent member similar to SwabCap® manufactured by ICU Medical, Inc. of San Clemente, California. The door 248 may hold the sanitizing agent-containing absorbent member in contact with the access port. The sanitizing agent, for example 70% isopropyl alcohol, sanitizes and then slowly evaporates. The continued presence of the absorbent member held by the door 248 maintains the sterility of the access port. The absorbent member is moved with the door 248 to allow access to the access port.

[0218] 35, a storage container 450 for housing a plurality of storage devices 200 is shown according to one embodiment or aspect. In some embodiments or aspects, the storage container 450 may be configured to house the storage devices 200 during shipping and storage prior to use. The storage container 450 has a housing 452 defining an interior 454 configured to receive a plurality of storage devices 200 therein. The housing 452 may have a housing portion 456 and a lid portion 458 connected to the housing portion 456 by a hinge 460. In some embodiments or aspects, the housing 452 of the storage container 450, such as at least one of the housing portion 456 and the lid portion 458, may provide additional shielding properties to enhance radiation shielding capabilities. In this manner, radiation emitted by therapeutic or diagnostic agents housed within the storage device 200 may be contained during shipping and storage.

[0219] After the therapeutic or diagnostic agent is expelled from the storage device 200 and injected into the patient, the material used to inject the therapeutic or diagnostic agent into the patient is collected for storage and disposal. With reference to FIG. 36, a waste container 462 is provided for containing such material. In some embodiments or aspects, the waste container 462 is configured to contain the storage container 200, the fluid cassette 300, and the infusion tube 406 used during the injection procedure. The waste container 462 has a housing 464 defining an interior 466 configured to receive the used storage container 200, the fluid cassette 300, and the infusion tube 406. In some embodiments or aspects, the housing 464 of the waste container 462 may provide shielding properties to provide radiation shielding capabilities. In this manner, radiation emitted by the used storage container 200, the fluid cassette 300, and the infusion tube 406 can be contained for safe disposal. In some embodiments or aspects, the waste container 462 can be configured to seal off the remaining fluid in the used storage container 200 , the fluid cassette 300 , and the infusion tube 406 .

[0220] 36, a label 474, optionally printed by the delivery system 100, may be affixed onto the disposal container 462 to prevent the disposal container 462 from being opened after used material has been placed therein. The label 474 may also provide information regarding when the material has been used and whether the disposal container 462 has been stored long enough for subsequent disposal. The label 474 may have a bar code or an RFID tag such that a bar code scanner or RFID reader can provide the disposal information to a computer in response to reading the label 474.

[0221] After the used material is placed in the labeled waste container 462, the waste container 462 may be temporarily stored on the cart of the delivery system 100. In some embodiments or aspects, the labeled waste container 462 may be stored in a waste locker 476 shown in FIG. 37. In some embodiments or aspects, the waste locker 476 may have multiple drawers or shelves 478 each configured to hold multiple waste containers 462. The label 474 on the waste container 462 may be scanned by a user with a mobile barcode reader. If the scanned barcode indicates that the material in the waste container 462 has decayed sufficiently that it is safe to discard, an alert, such as a message, sound and / or color, may indicate that the scanned waste container 462 may be removed from the waste locker 476 and disposed of using an approved disposal process.

[0222] In some embodiments or aspects, a drawer or shelf 478 of a waste locker 476 may have at least one indicator 480 (e.g., a red LED and a green LED) configured to indicate whether a particular waste container 462 on the drawer or shelf 478 is safe for disposal. For example, a user may scan a barcode of an individual waste container 462 and provide other input to an inventory control computer 482 to indicate that the individual waste container 462 has been added to a drawer or shelf 478. The inventory control computer 482 may then determine whether the stored material in each particular waste container 462 has sufficiently decayed based on the scanned information associated with the used material (e.g., date of use, etc.) to control the state of the at least one indicator 480. For example, the inventory control computer 482 can control the state of at least one indicator 480 so that an LED or other indicator means of at least one indicator 480 indicates (such as by displaying a red or other message) that the material in the waste container 462 is too radioactive to be discarded, or so that an LED or other indicator means of at least one indicator 480 indicates (such as by displaying a green or other message) that the material in the waste container 462 can be discarded. Such an indicia can allow a user to quickly determine whether the waste container 462 can be discarded. This can avoid the need for a user to periodically scan the container or check the use date on the label 474 of each waste container 462 to determine the waste status of the waste container 462.

[0223] The waste locker 476 may have a door 484 enclosing its interior and a locking mechanism 486 for locking the door 484. In some embodiments or aspects, the locking mechanism 486 may be configured such that only users with sufficient credentials can open the door 484 and access the waste locker 476. For example, the locking mechanism 486 may be such that a user must have a key to unlock the door 484 or a user badge or access rights associated with a user login that provides input to a controller to unlock the door 484.

[0224] Among the features, capabilities and advantages provided by the systems and methods described herein are the minimization of connections that must be made, the minimization of connections that must be separated or disconnected, and the containment of each connection as much as possible. In the use of some embodiments, methods or systems, the only connection that is separated is the connection to the patient, which is preferably done only after all drug has been delivered and the drug has been washed from the delivery connection. Thus, there is a very low probability of any drip, spill or leak of liquid drug, aerosol, vapor or gas being released that could pose a danger to the operator or others in the vicinity. Some radioactive daughter products are gases. Chemotherapy aerosols can be dangerous to people in the vicinity.

[0225] Referring to FIG. 38, an exemplary method for a test injection prior to delivery of a therapeutic or diagnostic agent is shown. At 500, a patient P is connected to the delivery system 100 via an infusion set 406, and the patient P is administered a test injection of saline or other fluid. For example, the injector 170 can be operated to fill the syringe 312 with saline or other fluid from the auxiliary fluid source 394 and deliver the test injection of saline or other fluid to the patient via the infusion set 406. The volume of saline or other fluid delivered to the patient can be sufficient to confirm whether the saline or other fluid is delivered to the patient's vasculature, extravasates, or leaks into the tissue. At 502, the patient P and an authorized user AU administering the procedure to the patient P confer whether the test injection of saline or other fluid was successful. For example, the authorized user AU may visually check the injection site for signs of extravasation and / or palpate the injection site. Patient P may report any discomfort associated with the test injection of saline or other fluid.

[0226] 38, at 504, the patient P is administered a pre-infusion of saline or other fluid. For example, the injector 170 may be operated to fill the syringe 312 with saline or other fluid from the auxiliary fluid source 394 and deliver a test injection of saline or other fluid to the patient via the infusion set 406 at a higher volume and for a longer duration than during the test injection at 500. In some embodiments or aspects, the injection volume, injection duration, and / or injection rate are selected to correspond to the injection volume, injection duration, and / or injection rate for delivery of a therapeutic or diagnostic agent. Studies have demonstrated that starting an injection with saline at the full injection rate reduces the likelihood of extravasation and allows time for extravasation to be sensed if extravasation is about to occur. At 506, the patient P is administered an injection of a therapeutic or diagnostic agent using a predetermined injection protocol. This method may be performed following a previous prounless pre-infusion unless the operator intervenes.

[0227] 39, an exemplary method for administering a therapeutic or diagnostic agent using the delivery system 100 is shown. At 510, the delivery system 100 is prepared for an administration procedure. For example, at 512, one or more storage devices 200 are loaded into one or more storage compartments 106 of the cart 102. At 514, the fluidic cassette 300 is loaded into the injector 170. For example, the fluidic cassette 300 is placed in the second drawer or shelf 110 of the cart 102 such that the fluidic cassette 300 engages with the injector 170. In some embodiments or aspects, an alignment element 370 on the fluidic cassette 300 is configured to engage with an alignment pin 176 of the fluidic injector (shown in FIG. 26) to position the fluidic cassette 300 relative to the injector 170 such that various components of the injector 170 can interface with corresponding components of the fluidic cassette 300.

[0228] 39, at 516, an auxiliary fluid supply 394 is connected to the fluidic cassette 300. For example, the auxiliary fluid supply 394 may be spiked and fluidly connected to the fluidic pathway set 314 of the fluidic cassette 300 via an auxiliary line 396 (shown in FIG. 31). At 518, the storage device 200 is connected to the fluidic cassette 300. In some embodiments or aspects, a label, tag, or other indicia 270 (shown in FIG. 16) on the storage device 200 may be scanned prior to or upon connection with the fluidic cassette 300 to load information regarding the contents of the storage device 200 into the controller 114.

[0229] At 520, the infusion set 406 is fluidly connected to the fluid pathway set 314 (shown in FIG. 31 ) of the fluid cassette 300, and the fluid pathway set 314 and the infusion set 406 are primed. In some embodiments or aspects, the controller 114 (shown in FIG. 5 ) of the delivery system 100 may be configured to initiate a priming procedure, where the syringe 312 operates to draw fluid from the auxiliary fluid source 394 into the fluid pathway set 314 and deliver the fluid into the infusion set 406 to prime the fluid pathway set 314 and the infusion set 406 with fluid.

[0230] 39, a test injection procedure is performed at 522. In some embodiments or aspects, the test injection procedure may include 500-504 described herein with reference to FIG.

[0231] At 524, the delivery system 100 is configured to administer a therapeutic or diagnostic agent to the patient. For example, the syringe 312 may be filled with a therapeutic or diagnostic agent from the container 226 of the storage device 200 and operated to deliver the therapeutic or diagnostic agent to the patient P via the infusion set 406 based on a predetermined administration protocol. In some embodiments or aspects, the delivery system 100 may be configured to administer a unit dose to the patient, where the unit dose requires the delivery of the entire contents of the container 226. In other embodiments or aspects, the delivery system 100 may be configured to administer a non-unit dose to the patient, where the non-unit dose requires the delivery of a portion of the entire contents of the container 226.

[0232] 39 , at 526, once the administration procedure is completed, the infusion set 406 is removed from the patient P and the assembly 150 of the storage device 200 and the fluid cassette 300 are removed from the injector 170. At 528, the used storage device 200, fluid cassette 300, and infusion set 406 are placed into a waste container 462 and a label 474 is applied to the waste container 462 before the waste container 462 is placed into temporary storage on the cart 102. For example, the waste container 462 may be placed in the third drawer or shelf 112 of the cart 102.

[0233] At 530, the procedure room is cleaned and the delivery system 100 can be prepared for another administration procedure. At 532, the waste container 462 is moved to a waste locker 476 for further in-situ decay of the radioactive material.

[0234] The use of labels, tags, or other indicia 270 on the storage device 200 for administration of new doses and storage of used material for disposal can also provide sufficient information to prompt ordering of new doses. For example, the inventory system can include a computer that receives information regarding the storage device 200 used, such as based on information contained in the label, tag, or other indicia 270 (shown in FIG. 16 ), and determines whether the number of available doses falls below a preselected threshold for triggering an order for additional doses, such as based on the number of available storage devices 200. Optionally, the inventory system may compare the number of available doses to the patient scheduled amount. In some circumstances, the inventory system can communicate this condition to the delivery system such that an automated message is sent to the customer to flag low inventory and prompt submission of a new purchase order for additional doses. The inventory system can include software configured to facilitate use of the inventory system. For example, the software can be configured to facilitate inventory management and ordering, generation / acceptance of written instructions, and generation of compliance reports. Additionally, the use of labels, tags, or other indicia 270 on the storage device 200 for administration of new doses and storage of used material for disposal can also provide sufficient information to facilitate billing for use of the drug and system, if that is a business mechanism.

[0235] Referring now to FIG. 40, a schematic diagram of a fluid injection system 1000 according to an embodiment of the present disclosure is shown. The system 1000 includes two fluid reservoirs 1020A, 1020B, which may be syringes as illustrated in FIG. 40. The first of the fluid reservoirs 1020A contains a therapeutic or diagnostic agent, such as a radiopharmaceutical drug, and the second of the fluid reservoirs 1020B contains a flushing agent, e.g., saline. Fluid may be injected from the fluid reservoirs 1020A, 1020B by respective plungers 1030A, 1030B, which are controlled by piston actuators 1040 operated by a system controller 9000. The system controller 9000 may control essentially all automated functions of the system 1000, and may further include or be connected to a user interface for receiving input from an operator. The system controller 9000 may include at least one processor for performing various functions of the system 1000 described herein. The system controller 9000 may further include a non-transitory computer-readable medium for storing instructions that, when executed by the at least one processor, cause the at least one processor to perform various functions of the system 1000 described herein. The system controller 9000 includes or interfaces with a user interface 9010. An on-site operator OP1 interacts with the system through the user interface 9010. The on-site operator may be an authorized user AU. The system may also communicate with one or more additional or auxiliary systems 9030, which may include, for example, an imaging system, a hospital information system, an electronic medical record system, an image storage system, a radiology information system, a nuclear medicine information system, cloud storage, cloud computing, and an ablation control system. As described, there are legal, regulatory, and procedural requirements regarding who is authorized to perform what aspects of drug preparation and delivery.Additional systems that may be accessed are local, regional, or national databases that may be used to verify license or entitlement to perform the method or function to be performed. The communication interface to the one or more additional systems 9030 may be through a user interface as shown, or directly from a system controller (not shown). Communications may utilize wired or wireless communications known to those skilled in the art, provided that communications may be fast enough to allow for effective interaction, operation, and, where applicable, control of the system.

[0236] In addition to the data, information, and communication systems, the additional system 9030 may be a medical patient measurement or monitoring system, such as an ECG, pulse oximeter, temperature, movement, hydration status, cardiac output, and / or respiratory rate. In some embodiments or aspects, the additional system 9030 may be, for example, a camera on a separate device that observes or monitors the patient. The data regarding the patient may be used to monitor the patient's condition, check for distress, and / or detect the occurrence of adverse events during the infusion, as described in WO 2021 / 222771, which is fully incorporated by reference herein. The additional system 9030 may also be a medical measurement system, such as a CT imager, an MR imager, an ultrasound unit, or a similar device that performs measurements on the patient. The additional system 9030 may be a medical output or treatment device that performs a function or action on the patient. Such a device may be, for example, one or more infusion pumps that inject flushing fluids, protective agents, and / or other drugs into different or the same IV of the patient. The infusion pump may inject additional saline with the goal of establishing a significant flow in and through the patient's veins to reduce the chance of retention in the veins. Significant flow in an adult is at least 0.1 ml / sec, preferably 0.5 ml / sec, and ideally 1.0 ml / sec, whether provided by an additional fusion pump or one or more pumps of the present disclosure. The flow rate that may be used is limited by the total desired time of infusion and the need to not overload the patient with fluid. In some cases, due to the risk of overloading with fluid, it may be desirable to split the administration into multiple separate boluses and to pause or reduce the flow of saline between the boluses. Each bolus is a bolus of drug followed by a wash bolus that washes the drug from the vicinity of the venous infusion site. In some embodiments, it is desirable for the additional system 9030 to communicate its status to the system controller 9000. It is further desirable for the controller 9000 to be able to activate, program, or control the additional system 9030 so that the entire infusion can be well coordinated.In embodiments in which the additional system 9030 is an infusion pump, the infusion pump may be used in the patency check procedure of FIG.

[0237] The fluid reservoirs 1020A, 1020B are fluidly connected to the patient P via a fluid path set 1010 comprising various fluid path elements. The fluid path set 1010 includes a T-junction 1012 where the outlet lines from the fluid reservoirs 1020A, 1020B join into a single line for delivery to the patient P. A valve 1014 is incorporated into or located upstream of the T-junction 1012 to prevent radiopharmaceutical from flowing through the T-junction 1102 during priming of the system 1000. Suitable embodiments of the valve 1014 include, for example, a check valve, a high crack pressure valve, or a stopcock. An example of a commercially available component that includes the T-junction 1012 and the valve 1014 is the SSIT-96LV sold by Bayer, AG. The various components of the system 1000 can be configured for single-patient use and / or multi-patient use. For example, portions of the fluid pathway set 1010 may be configured for single patient use or may be disposed of after each use. The fluid reservoirs 1020A, 1020B may be configured for single patient use or multi-patient use in various embodiments. Further details of single and multi-patient configurations of the various components in the system 1000 are described in U.S. Pat. Nos. 8,926,569, 9,855,390, 9,173,995, 9,700,670, 9,480,797, 10,039,889, 10,512,721, and 10,668,221, the disclosures of all of which are incorporated herein by reference in their entireties.

[0238] Continuing to refer to FIG. 40, the first fluid reservoir 1020A may be at least partially encased by a shield 2020 to protect the operator and patient from unwanted radiation exposure. The structure and material of the shield 2020 may be selected based on the radiation characteristics of the radiopharmaceutical contained in the first fluid reservoir 1020A, such as the type and amount of radiation emanating from the radiopharmaceutical and / or the quantity of the radiopharmaceutical. Exemplary types of radiation emitted are gamma rays, beta rays, alpha rays, and positrons. These types differ, for example, in their penetration of shielding and damage to tissue. The amount of radiation from a source is generally measured in units of decay per second or becquerels in the SI system of units. If the radiopharmaceutical is expected to emit a relatively large amount of highly penetrating radiation, the shield 2020 may be composed of a thick layer of lead or tungsten. If the radiopharmaceutical is expected to emit a relatively small amount of weakly penetrating radiation, the shield 2020 may be composed of a thin layer of plastic or only a distance. In other embodiments of the system 1000, the first fluid reservoir 1020A containing the radiopharmaceutical is located a predetermined safe distance away from the operator(s) and the patient(s), such as in a separate room, to eliminate unnecessary radiation exposure.

[0239] 40, some embodiments of the system 1000 include one or more radiation measuring sensors S1, S2 associated with the first fluid reservoir 1020A. The sensors S1, S2 are configured to generate and transmit to the system controller 9000 a signal (i.e., a voltage or digital signal) related to radiation emanating from and impinging on the first fluid reservoir 1020A. In some embodiments, one or more labels, tags, or data elements D1 associated with the first fluid reservoir 1020A include information about the contents of the first fluid reservoir 1020A, such as product information, production information, prescription information, shipping condition information, drug type, total dose, time the radiopharmaceutical was prepared, and time the dose was measured. The data elements D1 may also include information about the position of the plunger 1030A in the first fluid reservoir 1020A, and other relevant information about the injection procedure. Data element D1 interacts with the system controller 9000 to provide information to an operator, data system, or imaging system for use in subsequent calculations and / or communications. Data element D1 may be any type of data-containing device, such as a printed label, a bar code, or an electronically readable device, such as a radio frequency identification (RFID) tag. Data element D1 may contain information by itself (e.g., drug type, total dose, time the radiopharmaceutical was prepared, time the dose was measured, plunger position, etc.), or data element D1 may contain information such as an index or website address that directs the system controller 9000 to a location where the information can be retrieved, such as a secure central database. Data element D1 may be writable by the system controller 9000 to incorporate information during or after one or more injection procedures are being performed using the radiopharmaceutical contained in the first fluid reservoir 1020A. For example, the system controller 9000 may update data element D1 (or a central database indexed by data element D1) with the amount of radiopharmaceutical remaining, the position of plunger 1030A, or the number of patients injected.Some or all of the data element D1, sensors S1, S2, and shielding may be associated with the fluid reservoir 1020A and then shipped from the radiopharmaceutical pharmacy along with the drug for incorporation into the system 1000. Alternatively, some or all of the data element D1, sensors S1, S2, and shielding may be associated with the system 1000 independent of the fluid reservoir to be considered a permanent or semi-permanent part of the system 1000.

[0240] With continued reference to FIG. 40, the fluid path set 1010 includes one or more fluid path elements, e.g., tubes and valves, that carry fluid from the fluid reservoirs 1020A, 1020B to the patient P. One of the fluid path elements of the fluid path set 1010 may include a filter 3000 for selectively retaining radioactive particles from a radiopharmaceutical that passes through the filter 3000 on its way to the patient P. The particles may be, for example, atoms, molecules, chelates, aggregates, colloids, or other physical structures that include at least one radioactive atom. The filter 3000 is configured to selectively remove undesirable atoms or molecules and / or particles in the radiopharmaceutical and have no, minimal, or controlled effect on the clinical properties of the radiopharmaceutical that exits the filter. For example, the filter 3000 may be configured to remove radium from a conjugated thorium radiopharmaceutical. The presence of radium in conjugated thorium is described in US Patent Publication No. 2019 / 0002363, the disclosure of which is incorporated herein by reference in its entirety. In another example, the filter 3000 may be configured to capture and remove the originating isotope in the radiopharmaceutical. In such an example, the radiopharmaceutical may be provided to the first fluid reservoir 1020A, or the first fluid reservoir 1020A may include a generator that produces the radiopharmaceutical, such as a rubidium or technetium generator. Such generators are described in US Patent Publication No. 2005 / 0139994, the disclosure of which is incorporated herein by reference in its entirety. A filter similar to this may be configured to immobilize the originating isotope in a rubidium, gallium, or technetium generator. The filter 3000 may be constructed at least in part from materials similar or identical to those used for isotope immobilization in a rubidium, gallium, or technetium generator. Thus, any breakthrough of a quantity of the isotope from the generator is captured by the filter 3000.

[0241] 40, the system 1000 may include one or more sensors S3, S4, S5 associated with the fluid path set 1010 and in communication with the system controller 9000. For example, a filter radiation sensor S4 may be positioned proximate the filter 3000 to detect radiation buildup in or on a portion of the filter material and / or in the fluid path within the filter 3000. The fluid path radiation sensors S3, S5 may be positioned in association with the fluid path set 1010 upstream and downstream of the filter 3000, respectively. Thus, the fluid path radiation sensors S3, S5 may measure radiation within the fluid path set 1010 on either side of the filter 3000. The system controller 9000 may utilize measurements from sensors S3, S4, S5 to monitor radiation accumulation and delivery throughout the system 1000, evaluate the efficiency and sufficiency of filtration, and adjust or stop the injection procedure if radiation levels increase to a level that threatens the health of the patient or operator or otherwise deviate from expected radiation levels, e.g., if the radioactivity retained in the filter 3000 is too high.

[0242] To prepare the system 1000 for performing an injection procedure, the elements of the fluid pathway set 1010 are assembled in the general configuration shown in FIG. 40 and placed in operative association with the sensors S1-S5. In some embodiments, the fluid reservoirs 1020A, 1020B are supplied pre-filled with their respective fluids and connected to the fluid pathway set 1010. In some embodiments, the shield 2020 and optionally the sensors S1, S3, and the device D1 are supplied in association with a pre-filled syringe 1020A. In other embodiments, one or both of the fluid reservoirs 1020A, 1020B may be filled manually or automatically using additional components of the system 1000 (see, e.g., FIG. 44) prior to performing an injection procedure. In some embodiments, some or all of the fluid pathway elements may be pre-connected to simplify use and reduce the possibility of assembly errors.

[0243] After the system is assembled for use, operation is as follows: The assembled fluid path set 1010 is primed by pumping fluid from the fluid reservoirs 1020A, 1020B into the fluid path set 1010 to displace air prior to connection to the patient. Priming may be performed by advancing a plunger 1030A associated with the first fluid reservoir 1020A such that the portion of the fluid path set 1010 from the first fluid reservoir 1020A to the T-junction 1012 is filled with radiopharmaceutical. The valve 1014 is preferably closed to allow air to exit the fluid path elements between the first fluid reservoir 1020A and the T-junction 1012 and then prevents radiopharmaceutical from entering the portion of the fluid path set 1010 downstream of the T-junction 1012. After the portion of the fluid path set 1010 from the first fluid reservoir 1020A to the T-junction 1012 is primed with the radiopharmaceutical, the first plunger 1030A is stopped and the second plunger 1030B associated with the second fluid reservoir 1020B is advanced, thereby filling the remaining portion of the fluid path set 1010 with flushing agent, e.g., saline, from the second fluid reservoir 1020B. The second plunger 1030B is then stopped and the fluid path set 1010 is fully primed.

[0244] Once primed, the fluid pathway set 1010 may be connected to the patient P, for example, via a catheter 1016 of the fluid pathway set 1010 inserted into an intravenous administration site 1018 of the patient P. In other embodiments, the fluid pathway set 1010 may be indirectly connected to the intravenous administration site 1018 of the patient P via a temporary pump, as described herein with reference to Figures 42, 43, and 54. With further reference to the embodiment shown in Figure 40, once the fluid pathway set 1010 is primed and connected to the patient P, the system controller 9000 may automatically, or by manual input from an operator, actuate the piston actuator 1040 to effect delivery of the radiopharmaceutical and flushing agent, if prescribed for the injection procedure.

[0245] The system controller 9000 may determine the volume of the radiopharmaceutical to be delivered to the patient P based on the initial dose and volume or concentration of the drug in the first fluid reservoir 1020A, which is then corrected to account for any radioactive decay occurring to the radiopharmaceutical. The dose and concentration of the radiopharmaceutical may be known or derived from data stored in the memory of the system controller 9000, or the system controller 9000 may determine the dose or concentration from radiation measurements obtained by sensors S1, S2 associated with the first fluid reservoir 1020A. The system controller 9000 may determine the volume of the radiopharmaceutical in the first fluid reservoir 1020A based on the position of the first plunger 1030A, which may be obtained from data element D1 as described herein, or from sensors (e.g., encoders) associated with the piston actuator 1040 and / or the first plunger 1030A. Additional instructions for calculating the initial dose and volume or concentration of a radiopharmaceutical are provided in US Pat. No. 10,016,618, the disclosure of which is incorporated herein by reference in its entirety.

[0246] In some embodiments, the flushing agent may serve additional functions beyond priming the fluid pathway set 1010. The flushing agent may also be injected before the radiopharmaceutical as a test injection to ensure that the system components are connected as intended and / or that there is good flow from the catheter 1016 into the patient's vein and central circulation. The operator may then confirm with the patient that the flushing agent injection did not cause discomfort. The flushing agent may also be injected at the beginning of the injection to fully dilate the vein. The flushing agent may also be injected at least partially simultaneously with the radiopharmaceutical to facilitate flow of the radiopharmaceutical through the intravenous administration site 1018 or other port into the central circulatory system of the patient P, thus reducing residence time or exposure time for the injected drug. The flushing agent may also be injected subsequently after the injection of the radiopharmaceutical to ensure that all radiopharmaceutical that passes through the valve 1014 is flushed out of the fluid pathway set 1010 into the patient P, ensuring complete injection of the radiopharmaceutical dose.

[0247] Although system 1000 is generally described herein, further details of certain system components may be found in the corresponding component descriptions in U.S. Patent Application Publication No. 2008 / 0294096, U.S. Patent No. 9,005,166, U.S. Patent No. 7,713,232, U.S. Patent Application Publication No. 2021 / 0338922, International Patent Application Publication No. 2015 / 126526, U.S. Patent Application Publication No. 2021 / 0055431, U.S. Patent No. 9,002,438, U.S. Patent No. 7,813,841, U.S. Patent Application Publication No. 2018 / 0296751, and U.S. Patent Application Publication No. 2019 / 0307949, the disclosures of all of which are incorporated herein by reference in their entireties.

[0248] Referring now to FIG. 41, an exemplary graph 2000 of fluid delivery using the system 1000 of FIG. 40 is illustrated. In the graph 2000, the x-axis shows time and the y-axis shows a sensor output signal (e.g., voltage) corresponding to the detected radiation. It should be understood that the scale of the x-axis and y-axis is not necessarily linear and the units of the graphed values ​​are arbitrary. The purpose of FIG. 41 is to illustrate the relationship between time and measured radiation during any injection procedure, and the relative values ​​may not reflect the actual injection procedure performed by the system 1000. The sensor output of the actual radiation value depends heavily on the type and location of the sensors and electronics used in the system 1000, as well as the geometry of the fluid path elements of the fluid path set 1010. The time relationship between the various transitions of the radiation values ​​shown in FIG. 41 similarly depends on the geometry of the fluid path elements and the flow rates of the radiopharmaceutical and flushing agents that may vary during the injection. Additionally, while the depiction of the sensor output signal in graph 2000 assumes for simplicity that a "higher" sensor output corresponds to a higher radiation, this need not be true and the actual sensor used may, for example, exhibit an inverse relationship between output (e.g., voltage) and detected radiation. Nonetheless, graph 2000, together with all other graphs provided in the accompanying drawings, effectively illustrates the operating principles of system 1000.

[0249] 40 and 41, the time before T1 indicates a primed state of the system 1000 before the injection procedure is initiated. Thus, the output signals of the sensors S1 and S2 associated with the first fluid reservoir 1020A are substantially constant due to the presence of the radiopharmaceutical in the first fluid reservoir 1020A. The output signals of the sensors S3, S4, S5 are background or nominal values ​​indicating substantially zero radiation since the radiopharmaceutical has not advanced in the fluid path set 1010 beyond the T-junction 1012. At time T1, the piston actuator 1040 begins to advance the first plunger 1030A until the radiopharmaceutical upstream of the T-junction 1012 reaches a pressure sufficient to open the valve 1014. As the radiopharmaceutical is injected from the first fluid reservoir 1020A, the output signal of the sensor S1 begins to decrease (indicating a decrease in detected radiation). At time T2, the radiopharmaceutical advances through the fluid path set 1010 into the detection range of sensor S3. Thus, the output signal of sensor S3 begins to increase (indicating an increase in detected radiation). Similarly, at time T3, the radiopharmaceutical advances into the filter 3000 and enters the detection range of sensor S4. Thus, the output signal of sensor S4 begins to increase. At time T4, the first plunger 1030A displaces a sufficient volume of the radiopharmaceutical from the first fluid reservoir 1020A that the output signal from sensor S2 begins to decrease. At time T5, the radiopharmaceutical advances into the detection range of sensor S5. Thus, the output signal of sensor S5 begins to increase. After a certain injection time, generally indicated in time domain T6, the radiopharmaceutical reaches a substantially constant maximum flow rate through the fluid path set 1010 and the output signals from sensors S3, S5 reach a plateau (indicating a substantially constant level of detected radiation). The output signal of sensor S4 continues to increase in time domain T6, but at a relatively slower rate than the initial increase at time T3 as radioisotope impurities (or other filtered particles) accumulate in or on the filter 3000.

[0250] Once the desired amount of radiopharmaceutical has been transferred from the first fluid reservoir 1020A, the piston actuator 1040 begins to advance the second plunger 1030B to deliver the flushing agent from the second fluid reservoir 1020B. As the flushing agent advances through the fluid path set 1010 and displaces the radiopharmaceutical, the output signals of the sensors S3, S5 decrease in time domain T7 back to substantially zero (or near their respective background outputs prior to time T1). As the flushing agent flushes the radiopharmaceutical from the filter 3000, the output signal of the sensor S4 similarly decreases, but at least a portion of the trapped isotope impurity captured by the filter 3000 during delivery of the radiopharmaceutical remains. Thus, the output signal of the sensor S4 decreases to a substantially constant level indicative of the trapped isotope impurity at time T8.

[0251] Continuing to refer to FIG. 41, the sensor output signal during the injection procedure can be used to monitor the progress of the injection procedure. For example, the slope of the increase in the output signal from sensor S4 in the time domain T6 may be used as an indicator of proper system function or quality assurance indication. With knowledge of the decay series and half-life of the isotopes of the radiopharmaceutical, the time when the radiopharmaceutical was first prepared with a given amount of the desired isotope, and the known, small amount or complete absence of daughter or parent isotopes, it is possible to calculate the amount of one or more isotopes expected to be present in the radiopharmaceutical. Thus, the expected rate of increase of the daughter or parent isotope in the filter 3000 as a function of the volume of the radiopharmaceutical that has flowed through the filter 3000 can be calculated by the system controller 9000. The expected rate of increase of the daughter or parent isotope can then be compared to the actual rate of increase of the impurity isotope (as measured by sensor S4) to monitor the progress of the injection procedure. If the actual rate of increase of the impurity isotope deviates from the expected rate of increase of the impurity isotope by a predetermined amount or gradient, the system controller 9000 may alert an operator to the situation, and either the operator or the system controller 9000 may take appropriate corrective action. As discussed herein, the decay series and half-lives of the isotopes of the radiopharmaceutical, the time the radiopharmaceutical was originally prepared with a given amount of the desired isotope, and other information used in calculating the expected rate of increase of the impurity isotope may be stored in data element D1, retrieved by the system controller 9000 using data element D1, or communicated to the system controller 9000, or calculated by it from data stored in the system controller 9000.

[0252] An increase in the output signal of sensor S4 at a rate lower than the calculated expected increase may be an indication that an insufficient amount of daughter or parent is being removed by the filter 3000. An increase in the output signal of sensor S4 at a rate higher than the calculated expected increase may indicate that there is a problem with the initial measurement of radiation, or that an undesirable amount of radiopharmaceutical is being removed from the fluid pathway set 1010 by the filter 3000. In either case, the system controller 9000 may alert the operator of the situation, and either the operator or the system controller 9000 may take appropriate corrective action, such as pausing or terminating the injection procedure.

[0253] The output signal of sensor S4 at time T8 may also be used as an indicator of proper system function or a quality assurance indication. For example, the output signal of sensor S4 at time T8 may be used to determine whether an adequate amount of isotopic impurities has been removed and whether an adequate amount of radiopharmaceutical has been delivered to a patient (or to an interim pump or container as shown and described in connection with Figures 42, 43, and 54). The expected amount of isotopic impurities may be derived from known information such as the decay series and half-lives of the isotopes of the radiopharmaceutical, and the time the radiopharmaceutical was originally prepared with a given amount of the desired isotope.

[0254] In embodiments where the radiopharmaceutical is supplied from a generator, such as a rubidium, gallium or technetium generator, the output signal of sensor S4 may be used to identify the breakthrough of the parent isotope from the generator. In particular, a too high rate of increase in the output signal of sensor S4 in time domain T6 or a too high residual output signal of sensor S4 in time domain T8 may indicate the breakthrough of the parent isotope from the generator. The system controller 9000 may be configured to generate a warning to inform the operator to stop using the generator. Examples of systems including a generator for generating radiopharmaceuticals include U.S. Pat. No. 7,813,841, U.S. Patent Application Publication No. 2018 / 0296751, and U.S. Patent Application Publication No. 2019 / 0307949, the disclosures of which are incorporated herein by reference in their entireties.

[0255] A variety of sensors may be used as sensors S1-S5. Examples include, but are not limited to, diode detectors, Geiger counters, solid-state pulse counters, ion chambers, scintillators with photodiodes (e.g., avalanche photodiodes), and SPECT or PET cameras. Alternatively, sensors S1-S5 may be more complex devices such as survey meters, electronic dosimeters, and various commercial products from Lucerno Dynamics®. Further details of some of these types of sensors are described in U.S. Pat. No. 9,002,438 and U.S. Patent Application Publication No. 2021 / 0055431, the disclosures of which are incorporated herein by reference in their entireties. The method of operation of sensors S1-S5 may be of varying sophistication, including binary sensing, counting or count rate sensing, dose or dose rate sensing, or energy or spectral sensing. In some embodiments, any of sensors S1-S5 may be an energy discriminating sensor, which may be able to quantify and distinguish radiation measurements of one or more of the isotopes involved by measuring the energy of the radiation. Sensors S1-S5 may be configured to detect (directly or via bremsstrahlung) various types of radiation associated with the injected radiopharmaceutical, e.g., alpha, gamma, neutrons, and beta radiation. Sensors S1-S5 may have detection ranges, or sensing areas, corresponding to a surface beneath the sensor, a segment of tubing of known volume, or an entire fluid path element (e.g., filter 3000). Sensors S1-S5 need not all be of the same type and configuration, and in fact it may be beneficial to use sensors of different types / configurations to measure radiation at different locations within system 1000.

[0256] While the embodiment shown in FIG. 40 includes five sensors, additional sensors may be used for redundancy to improve safety and reliability or to measure radiation at additional locations of interest. Alternatively, fewer than five sensors may be utilized. For example, in some embodiments, sensors S1, S2 associated with the first fluid reservoir 1020A may be eliminated by relying on initial calibration and content information of the first fluid reservoir 1020A. As discussed herein, such information may be included in (or may be obtained using) data element D1, allowing the system controller 9000 to implement or derive this information. In some embodiments, sensors S3, S5 may be eliminated and only sensor S4 may be used to detect radiation near the filter 3000. Alternatively, sensor S4 may be eliminated and the amount of isotope removed from the fluid path set 1010 by the filter 3000 may be calculated based on the output signals of sensors S3, S5 and the known flow rate of fluid passing through the filter 3000. As noted elsewhere, radiation in the radiopharmaceutical can be calculated from the initial calibration of the radiopharmaceutical in the radiopharmaceutical pharmacy and the time since that calibration. While it is possible to reduce the number of sensors for reasons discussed above, multiple sensors can provide redundancy and the ability to detect faults that cannot be predicted or detected by calculation. Examples of such faults include leaks or blockages in system components, malfunction of one of the fluid delivery devices (e.g., plungers 1030A, 1030B or piston actuator 1040), or other failure of elements of the fluid path set 1010. As noted above, any of the sensors S1-S5 may be energy discriminatory sensors that may be able to distinguish and quantify the radiation measurements of one or more of the isotopes involved by measuring the energy of the radiation. This has the advantage of reducing the number of sensors required or providing further information for calculations, evaluation of system behavior, filtration / removal, and / or ultimately increasing confidence in the quality of the radiopharmaceutical output by the system.

[0257] 42, another embodiment of the fluid injection system 1000 may include an interim pump or fluid reservoir 1020C into which the prescribed dose of radiopharmaceutical and flushing agent are pumped from the first and second fluid reservoirs 1020A, 1020B prior to delivery to the patient. In the event of a failure in the dose of radiopharmaceutical to be delivered, the failed dose is contained within the interim fluid reservoir 1020C and removed therefrom by the system 1000 or an operator without being delivered to the patient. The interim fluid reservoir 1020C illustrated in FIG. 42 is a syringe driven by a plunger 1030C in the same manner that the first and second fluid reservoirs 1020A, 1020B are driven by respective plungers 1030A, 1030B. The plunger 1030C associated with the interim fluid reservoir 1020C may be controlled by the same piston actuator 1040 as the plungers 1030A, 1030B or by an independent piston actuator. A pair of radiation sensors S1', S2' may be associated with the interim fluid reservoir 1020C and may be functionally similar to the radiation sensors S1, S2 associated with the first fluid reservoir 1020A. The system controller 9000 may determine and verify the dose or concentration of the radiopharmaceutical delivered to the interim fluid reservoir 1020C from the radiation measurements obtained by the sensors S1', S2'. Based on the radiation measurements obtained by the sensors S1', S2', the system controller 9000 may detect a malfunction of the dose delivered to the interim fluid reservoir 1020C. If such a malfunction is detected, the system controller 9000 may stop the injection procedure and alert the operator that the temporary fluid reservoir 1020C should be removed and discarded. If no malfunction is detected, the system controller 9000 may proceed with the injection procedure by actuating the plunger 1030C to inject a dose from the temporary fluid reservoir 1020C into the patient P.

[0258] 42, the interim fluid reservoir 1020C may be at least partially enclosed by a radiation shield 2020′ similar to the shield 2020 associated with the first fluid reservoir 1020A. A data element D1′ may also be associated with the interim fluid reservoir 1020C, similar to the data element D1 associated with the first fluid reservoir 1020A.

[0259] 43, another embodiment of the fluid injection system 1000 may include an interim pump or fluid reservoir 1020C into which the prescribed dose of radiopharmaceutical and flushing agent is injected from the fluid reservoir 1020B prior to delivery to the patient. In the event of a failure in the dose of radiopharmaceutical to be delivered, the failure dose is contained within the interim fluid reservoir 1020C and removed therefrom by the system 1000 or an operator without being delivered to the patient. The interim fluid reservoir 1020C illustrated in FIG. 43 is a syringe driven by a plunger 1030C in the same manner as the fluid reservoirs 1020B are driven by their respective plungers 1030B. The plunger 1030C associated with the interim fluid reservoir 1020C may be controlled by the same piston actuator 1040 as the plunger 1030B or by a separate piston actuator. A pair of radiation sensors S1', S2' may be associated with the interim fluid reservoir 1020C and may be functionally similar to the radiation sensors S1, S2 associated with other embodiments of the present invention. The system controller 9000 may determine and verify the dose or concentration of the radiopharmaceutical delivered to the interim fluid reservoir 1020C from the radiation measurements obtained by the sensors S1', S2'. Based on the radiation measurements obtained by the sensors S1', S2', the system controller 9000 may detect a malfunction of the dose delivered to the interim fluid reservoir 1020C. If such a malfunction is detected, the system controller 9000 may stop the injection procedure and alert the operator that the interim fluid reservoir 1020C should be removed and discarded. If no malfunction is detected, the system controller 9000 may proceed with the injection procedure by actuating the plunger 1030C to inject the dose from the interim fluid reservoir 1020C into the patient P.

[0260] 43, the temporary fluid reservoir 1020C may be at least partially enclosed by a radiation shield 2020' similar to the shield 2020 associated with the first fluid reservoir 1020A. A data element D1' may also be associated with the temporary fluid reservoir 1020C, similar to the data element D1 associated with other embodiments of the present invention.

[0261] 44, another embodiment of a fluid injection system 1000 includes a bulk source 1012A of a radiopharmaceutical to be administered to a patient P, or to multiple patients. The bulk source 1012A may be at least partially enclosed by a radiation shield 2220 similar to the shield 2020 associated with the first fluid reservoir 1020A. The bulk reservoir 1012A may be a storage container 200 having a volume sufficient for multiple doses. A valve Va, such as a stopcock, may be opened by the system controller 9000 to allow the first plunger 1030A to draw the radiopharmaceutical from the bulk source 1012A into the first fluid reservoir 1020A. The volume of the radiopharmaceutical dose drawn into the first fluid reservoir 1020A may be calculated based on the initial dose and volume or concentration of the radiopharmaceutical in the bulk source 1012A and the time of measurement of the initial dose and volume or concentration. By knowing the decay constants of one or more isotopes in the radiopharmaceutical, the volume of radiopharmaceutical to be delivered can be calculated based on the decay from the time the radiopharmaceutical was first measured to the present. Any or all of this information can be stored in data element D2 associated with the bulk source 1012A and accessible by the system controller 9000. Like data element D1 associated with the first fluid reservoir 1020A, data element D2 can be any type of data-containing device, such as a printed label, a bar code, or an electronically readable device, such as a radio frequency identification (RFID) tag. Sensors S1, S2 associated with the first fluid reservoir 1020A can be used as a surrogate or confirmatory measurement of the dose of radiopharmaceutical drawn from the bulk source 1012A to the first fluid reservoir 1020A.

[0262] In the embodiment shown in FIG. 44, some of the components of the system 1000 are configured for single-patient use and are disposed of per patient, while other components are configured for multi-patient use. A connector C1 disposed within the fluid pathway set 1010 provides a sanitary connection between the multi-patient component and the single-patient component. The multi-patient component includes a first fluid reservoir 1020A, a bulk fluid source 1012A, a valve Va, a connector C1, and a portion of the fluid pathway set 1010 upstream of the connector C1. The fluid pathway set 1010 downstream of the connector C1 is a single-patient component. Exemplary fluid pathway configurations including single-patient and multi-patient components are described in U.S. Patient Specific Dosing (ACDS) ... The single-use fluid pathway set 1010 may include two check valves (not shown) somewhere along its length as a cross-contamination prevention mechanism. Connector C1 may be a swabbable valve or connector as described in International Patent Application Publication Nos. WO 2013 / 059563 and WO 2014 / 210418, the disclosures of which are incorporated herein by reference in their entireties. The single-use fluid pathway set 1010 may extend all the way upstream and include a fluid reservoir 1020A. In this case, connector C is on the fluid pathway between a bulk fluid reservoir 1012A and, in this case, a single-patient fluid reservoir 1020A.Other components of the fluid injection system 1000 of Figure 44 that are not specifically described are assumed to be similar to the corresponding components of the embodiment of Figure 40. In some embodiments, the system 1000 shown in Figure 44 may include other components from Figure 40 that are not shown for simplicity, such as the filter 3000 and associated sensors S3-S5, as well as a second fluid reservoir 1020B that contains a flushing agent.

[0263] Referring now to FIG. 45, another embodiment of the fluid injection system 1000 is configured for single patient use. The volume of radiopharmaceutical to be delivered may be calculated based on the initial dose and the volume or concentration in the first fluid reservoir 1020A, with decay being corrected to provide the patient with the prescribed dose. The sensors S1, S2 may optionally be used to determine the dose or concentration in the first fluid reservoir 1020A. Similar to the embodiment of FIG. 40, the system controller 9000 may be configured to determine the volume of the radiopharmaceutical in the first fluid reservoir 1020A based on the position of the first plunger 1030A in the first fluid reservoir 1020A. Further aspects of this calculation are described in U.S. Pat. No. 10,016,618, the disclosure of which is incorporated herein by reference in its entirety. In some embodiments, the system 1000 shown in FIG. 45 may include other components from FIG. 40 that are not shown for simplicity, such as the filter 3000 and associated sensors S3-S5.

[0264] 45, the system controller 9000 may be configured to calculate the volume of radiopharmaceutical to be delivered to the patient P and thus the required travel distance of the first plunger 1030A. The calculation of the volume of radiopharmaceutical to be delivered includes the volume required to fill the fluid path set 1010 between the first fluid reservoir 1020A and the patient P. The length and volume of the fluid path set 1010 may be known or may be obtained, for example, by scanning data elements associated with the fluid path set 1010. To reduce radiopharmaceutical waste, the volume of the fluid path set 1010 may be minimized by using small diameter tubing. For example, the fluid path set 1010 may be constructed from PE10 tubing having an inner diameter of approximately 0.28 millimeters (0.011 inches).

[0265] FIG. 46 illustrates another embodiment of the fluid injection system 1000 similar to the embodiment of FIG. 45 but including a second fluid reservoir 1020B containing a flushing agent. The flushing agent may be injected to prime the fluid pathway set 1010, for example, as described herein with reference to the embodiment of FIG. 40. The flushing agent may also be injected before the radiopharmaceutical as a test injection to ensure that the system components are connected as intended. The flushing agent may also be injected at least partially simultaneously with the radiopharmaceutical to facilitate flow of the radiopharmaceutical through the intravenous administration site 1018 or other port into the central circulatory system of the patient P. The flushing agent may also be injected subsequently after the injection of the radiopharmaceutical to ensure that all the radiopharmaceutical that passes through the valve Vc, which may be a check valve, crack pressure valve, or stopcock, is flushed out of the fluid pathway set 1010 and into the patient P to ensure complete injection of the radiopharmaceutical. In some embodiments, the system 1000 shown in FIG. 46 may include other components from FIG. 40 that are not shown for simplicity, such as the filter 3000 and associated sensors S3-S5.

[0266] FIG. 47 illustrates another embodiment of a fluid injection system 1000 including at least one radiation sensor S6 associated with a patient P, for example, proximate an intravenous administration site 1018 where the radiopharmaceutical is injected. In some embodiments, the system 1000 may also include sensor S3 (and / or other sensors S4, S5) described herein with reference to FIG. 40. Sensor S6 is used to detect conditions such as retention of the radiopharmaceutical at or near the intravenous administration site 1018 and / or to detect extravasation of the radiopharmaceutical into the surrounding tissues of the patient P. Further details of methods for detecting retention and extravasation are described herein with reference to FIGS. 48-53. In some embodiments, the system 1000 shown in FIG. 47 may include other components from FIG. 40 that are not shown for simplicity, such as a filter 3000.

[0267] 48 and 49 illustrate an example of the use of the system 1000 of FIG. 47. FIG. 48 shows a graph 2100 of fluid injection over time. Time in arbitrary units is graphed on the x-axis, and the portions that make up each total fluid delivery injection are graphed on the y-axis. The flushing agent is represented by the dotted area, and the radiopharmaceutical is represented by the shaded area. Starting at time T0 and proceeding to time T1, an initial injection phase is performed using the entire flushing agent to ensure that the system 1000 is connected and functioning as intended, and to fill the patient's vein. During the initial injection phase, the operator may manually verify that the flow rate is high enough by placing his or her finger near the intravenous administration site 1018 (see FIG. 47) of the patient P to feel the flow. Alternatively, or in addition, the operator may palpate to ensure that there is no swelling under the patient's skin that may indicate extravasation of the flushing agent. Good flow from the injected container may also be confirmed by the absence of significant back pressure on the second fluid reservoir 1020B during the test injection.

[0268] With continued reference to FIG. 48, at time T1, the injection of the radiopharmaceutical is initiated and the radiopharmaceutical begins to flow through the fluid pathway set 1010. In some embodiments, the injection at this stage is entirely radiopharmaceutical, or as shown in FIG. 48, the injection can be a mixture of radiopharmaceutical and flushing agent. The simultaneous injection of the flushing agent can, for example, facilitate the flow of the radiopharmaceutical through the fluid pathway set 1010 and the patient P to ensure rapid and complete delivery of the radiopharmaceutical. The simultaneous injection of the flushing agent can, for example, ensure that the radiopharmaceutical is flushed from the intravenous administration site 1018 into the central circulation of the patient P. The simultaneous injection of the flushing agent can also reduce adverse effects that the radiopharmaceutical may have on the patient P's blood vessels as the radiopharmaceutical passes through the patient P's blood vessels in a more concentrated form. At time T4, the injection of the radiopharmaceutical is complete and the injection proceeds with substantially 100% flushing agent to flush the radiopharmaceutical from the fluid pathway set 1010 and the patient P's veins. In some embodiments, particularly for imaging procedures, the volumetric flow rate of the flushing agent during the flushing operation is substantially the same as the total volumetric flow rate during the radiopharmaceutical injection (including the volumetric flow rate of any flushing agent delivered simultaneously with the radiopharmaceutical). Further details of the relationship between the volumetric flow rates during drug injection and subsequent flushing are described in U.S. Pat. No. 10,933,186, the disclosure of which is incorporated herein by reference in its entirety. For purely therapeutic procedures, maintaining a constant volumetric flow rate between the injection and flushing phases is not necessarily important, but may still be desirable.

[0269] 49, a graph 2200 of the sensor output signals of sensors S3, S6 shown in FIG. 47 is shown on the same timeline as graph 2100 in FIG. 48. At time T2, some time after the start of the radiopharmaceutical injection at time T1 in FIG. 48, the radiopharmaceutical advances within the fluid path set 1010 into the detection range of sensor S3. Thus, the output signal of sensor S3 begins to increase (indicating an increase in detected radiation). After this initial rise, the output signal of sensor S3 subsequently reaches a plateau when the fluid path set 1010 within the detection range of sensor S3 is filled with the maximum concentration of the radiopharmaceutical. As described herein, the system controller 9000 may be configured to determine the expected radiation using known information such as the volume of the fluid path set 1010 and the flow rate, concentration, and decay rate of the radiopharmaceutical. If the radiation detected by sensor S3 deviates sufficiently from the expected time course for the radiation, the system controller 9000 may indicate an error and alert the operator. This condition may be caused, for example, by a fault in the piston actuator 1040 or a leak in the fluid path set 1010, or an incorrect initial calibration date stored in, for example, D1.

[0270] 49, at time T3, the radiopharmaceutical reaches the patient P and is within the detection range of sensor S6. The output signal of sensor S6 begins to rise, indicating that the radiopharmaceutical is being delivered to the patient P. If, after a predetermined time interval, the system controller 9000 does not receive an output signal from sensor S6 indicating that the radiopharmaceutical has reached the patient P, the system controller 9000 may stop the injection procedure and alert the operator of a possible malfunction. At time T5, some time after time T4 in FIG. 48, the output signal of sensor S3 decreases as the radiopharmaceutical is flushed out of the fluid pathway set 1010 and thus out of the detection range of sensor S3.

[0271] Continuing to refer to FIG. 49, during a normal injection procedure, the output signal of sensor S6 follows the time course of the solid line labeled "S6 normal". In particular, the output signal of sensor S6 rises when the radiopharmaceutical reaches the patient P and is therefore within the detection range of sensor S6. The output signal of sensor S6 then reaches a plateau as the radiopharmaceutical reaches the maximum prescribed flow rate, and then decreases to a total body distribution value beginning at T6. When the radiopharmaceutical has been completely flushed from the intravenous administration site 1018, at time T7, the output signal from sensor S6 may remain at the total body distribution value. When sensor S6 is located downstream of sensor S3, the output signal of sensor S6 generally rises, reaches a plateau, and decreases with a time lag relative to sensor S3. The exact amplitude of the output signal of sensor S6 depends on many factors, such as the flow rate and volume of the fluid path elements, the location of sensor S6 relative to the intravenous administration site 1018 or other patient vessel or portion, the path of the container or port, and the depth of the container or port.

[0272] Continuing to refer to FIG. 49, the system controller 9000 may monitor the output signal of sensor S6 to detect anomalies in the delivery of the radiopharmaceutical. For example, the output signal of sensor S6 may be used to determine that extravasation or partial extravasation has occurred. In the event of extravasation, the output signal of sensor S6 may follow the time course of the dashed line labeled "S6 Extravasation." Following an expected initial rise in the output signal corresponding to the radiopharmaceutical first reaching the patient, the output signal of sensor S6 continues to rise during the injection rather than plateauing as would be expected. In addition, the output signal of sensor S6 shows little or no decrease once the injection of the radiopharmaceutical is terminated at time T6. The lack of decrease in the output signal of sensor S6 after time T6 indicates that the radiopharmaceutical is not being flushed out of the patient by the injection of the flushing agent. Additionally, the output signal of sensor S6 may remain the same magnitude after T7, when the radiopharmaceutical is expected to have been completely flushed from the intravenous administration site 1018, indicating that the radiopharmaceutical has extravasated into the tissue surrounding the intravenous administration site 1018. The amount of extravasated radiopharmaceutical may be the total volume injected or a portion of the injected volume. Additional methods of extravasation monitoring that may be implemented in system 1000 are described in International Patent Application Publication No. WO 2021 / 222771, the disclosure of which is incorporated herein by reference in its entirety.

[0273] Continuing to refer to FIG. 49, the system controller 9000 may also monitor the output signal of sensor S6 to detect retention (i.e., stasis or delayed clearance) of some or all of the radiopharmaceutical in the patient. In the case of retention, most or all of the radiopharmaceutical is successfully injected into the patient's blood vessel or port, but the natural flow in the blood vessel and the rate of injection are insufficient to advance the radiopharmaceutical into the patient's central circulation. Thus, the radiopharmaceutical accumulates at the intravenous administration site 1018 or at another location in the blood vessel. In this situation, the output signal of sensor S6 may follow the time course of the dashed-dotted line labeled "S6 Stasis, Slow, or Delayed Clearance" in FIG. 49. The output signal of sensor S6 increases during injection even after the radiopharmaceutical reaches its maximum flow rate, similar to that observed during extravasation. Although the slope of the increase shown in FIG. 49 may be less than that of extravasation in the case of retention because some drug flows downstream into the central circulation, it may not be possible in practice to distinguish between venous retention and extravasation based solely on the increase in the output signal of sensor S6. The slope representing venous retention in one patient may be the same as the slope of extravasation in a different patient, for example, due to the many differences in the patient's arms, veins, and sensor placement. After the injection is complete, the output signal of sensor S6 decreases at time T6 as the radiopharmaceutical is flushed out of the patient's blood vessel or port. However, the decrease in the output signal of sensor S6 occurs more slowly than during a normal injection and more rapidly than during complete extravasation, which may not decrease at all. In addition, there may be cases (not shown) where some radiopharmaceutical has extravasated and some is just slow to exit the vein. After determining that radiopharmaceutical extravasation or retention is occurring, the system controller 9000 may take further steps to assess the patient's situation and may alert the operator so that corrective measures can be initiated if necessary.

[0274] 50-53, sensors S3, S6 may also be used to identify extravasation or retention (i.e., clearance delay) before the full dose of radiopharmaceutical is delivered so that corrective action can be taken and / or the injection procedure can be appropriately stopped. FIG. 50 and FIG. 51 illustrate a graph 2300 of fluid injection over time and a graph 2400 of sensor response over time, respectively, according to one such embodiment of operating the system of FIG. 47. A test injection of radiopharmaceutical is given, e.g., a predetermined amount of 5%-20% of the total dose, and the response to the test injection is evaluated before delivering the remainder of the radiopharmaceutical dose. This test volume is exemplary and is selected to be large enough to be reliably measured by the sensor, and thus will depend on the particular sensor selected. To minimize harm to the patient if extravasation occurs, it is desirable to keep the volume low enough to be reliably measured by the sensor. Similar to the embodiment shown in FIG. 48, starting at time T0 and proceeding to time T1, a test injection is performed using the entire flushing agent to ensure that the system 1000 is connected and functioning as intended. At time T1, injection of the radiopharmaceutical begins, also similar to the embodiment shown in FIG. 48. At time T2, the output signal of sensor S3 increases as the radiopharmaceutical enters the detection range of sensor S3. At time T3, the output signal of sensor S6 increases as the radiopharmaceutical enters the corresponding detection range of the patient P and sensor S6. Because only a test injection of the radiopharmaceutical (e.g., 5%-20% of the total dose) is initially delivered, the size of the radiopharmaceutical bolus in the fluid pathway set 1010 and / or patient P may not be large enough to cause a plateau in the output signals of sensors S3, S6 as observed during a full dose injection (as shown in FIGS. 48 and 49). Rather, as shown in Figures 50 and 51, the output signals of sensors S3, S6 may reach a peak value and then begin to decrease as soon as the radiopharmaceutical is flushed from the system 1000. In other embodiments, a plateau in the sensor output signal may still occur, but the plateau may exist for a shorter period of time as compared to the full dose injection shown in Figures 48 and 49.

[0275] After the test injection of the radiopharmaceutical is injected, a flushing agent is then injected to flush the radiopharmaceutical from the test injection, and the output signals of sensors S3, S6 are monitored for signs of radiopharmaceutical extravasation and / or retention. In the absence of extravasation or retention, the output signal of sensor S6 decreases to a systemic distribution value after the test injection of the radiopharmaceutical is flushed, for example, by time T7. This behavior is illustrated by the solid line time course labeled "S6 Normal" in FIG. 51. In comparison, little or no significant decrease in the output signal of sensor S6 at time T7 indicates the presence of an extravasation condition, as shown by the dashed line time course labeled "S6 Extravasation." Similarly, a decrease in the output signal of sensor S6 at time T7 later than would be expected from a normal injection, as shown by the dashed line time course labeled "S6 Stasis, Clearance Delay," indicates the presence of a retention condition.

[0276] The system controller 9000 may use a predetermined threshold on the rate of decline of the output signal of the sensor S6 to distinguish between normal injection, holdup (i.e., clearance delay), and extravasation. The system controller 9000 may alert the operator accordingly. In the case of normal flow through the system, the system controller 9000 may proceed with injection of the remaining dose of radiopharmaceutical, either automatically or upon input from the operator. In the case of holdup (i.e., clearance delay), the system controller 9000 may still proceed with injection of the remaining dose of radiopharmaceutical, either automatically or upon input from the operator, but a modification of the injection procedure may be implemented to address the holdup condition. For example, the system controller 9000 may reduce the drug injection flow rate while maintaining the total volumetric flow rate to facilitate clearance and reduce accumulation of the radiopharmaceutical in the patient's blood vessels. Alternatively, the system controller 9000 may increase the flushing agent injection rate to facilitate clearance and reduce accumulation of the radiopharmaceutical in the patient's blood vessels. If extravasation is detected, the system controller 9000 may abort the injection procedure, either automatically, or upon input from the operator. The operator may then attempt to find a new intravenous administration site 1018, or wait until another time or day to retry the injection.

[0277] 52 and 53 show graphs 2500, 2600 illustrating another embodiment of the operation of the system 1000 of FIG. 47. As shown in graph 2500 of FIG. 52, the delivery of the radiopharmaceutical is divided into multiple stages. A first stage of the radiopharmaceutical injection occurs between times T1 and T4, and a second stage of the radiopharmaceutical injection occurs between times T6 and T10. The volume of the radiopharmaceutical injected during the first stage can be large enough to be reliably detected by the sensor and low enough not to cause harm to the patient in case of extravasation. Although the embodiment of FIG. 52 and FIG. 53 shows two stages of the pharmaceutical injection, any number of stages may be used. Similar to the embodiment described in FIG. 48-FIG. 51, a short injection of a flushing agent begins at time T0. The first stage of the radiopharmaceutical injection then begins at time T1, which optionally includes an injection of a flushing agent injected simultaneously with the radiopharmaceutical. As the radiopharmaceutical advances through the fluid pathway set 1010 and into the detection range of sensor S3, at time T2 the output signal of sensor S3 begins to rise before reaching a plateau, similar to that described in connection with Figure 49. Similarly, at time T3 the output signal from sensor S6 begins to rise as the radiopharmaceutical advances into the patient P and into the detection range of sensor S6. At time T4 the first stage of the radiopharmaceutical injection is completed. When the output signal of sensor S6 reaches a plateau and is no longer rising, the system controller 9000 determines that the injection is proceeding normally and may continue with the next radiopharmaceutical injection at time T6.

[0278] However, if at time T4 the output signal of sensor S6 continues to rise, the system controller 9000 may determine that either a retention (i.e., slow clearance) or extravasation condition exists because the radiopharmaceutical has not been flushed out of the detection range of sensor S6 by the flow of flushing agent injected after time T4. As described herein, it is difficult to determine in advance whether the sustained increase in the output signal of sensor S6 after time T4 is due to extravasation or slow clearance. To make a final determination, the system controller 9000 may inject a flushing agent between times T4 and T6 while monitoring the output signal of sensor S6. A decrease in the output signal of sensor S6 during the injection of the flushing agent between times T4 and T6 indicates that the radiopharmaceutical is being flushed out of the patient P and thus the current condition is retention rather than extravasation. The plateau in the output signal of sensor S6 during injection of flushing agent between times T4 and T6 indicates that the radiopharmaceutical is not being flushed out and thus extravasation is occurring.

[0279] If an extravasation condition is determined to exist, the system controller 9000 may abort the injection procedure and / or alert the operator. If retention is determined to exist, the system controller 9000 may alert the operator and proceed, either automatically or under operator guidance, with the second stage of injection of the radiopharmaceutical at time T6. To mitigate further retention of the radiopharmaceutical during the second stage of fluid injection, the system controller 9000 may modify the prescribed injection procedure by reducing the injection flow rate of the radiopharmaceutical and / or by increasing the co-injection of a flushing agent, as described in connection with FIG. 51.

[0280] As the second stage of the injection progresses, the system controller 9000 continues to monitor the output signal of the sensor S6 to monitor for extravasation, beginning at time T6. Even if extravasation did not occur during the first stage of the radiopharmaceutical injection, it is still possible that extravasation may occur during a subsequent stage of the radiopharmaceutical injection. At time T7, the output signal of the sensor S3 begins to rise as the radiopharmaceutical re-enters the detection range of the sensor S3. Similarly, at time T8, the output signal of the sensor S6 begins to rise as the radiopharmaceutical re-enters the detection range of the sensor S6. During a normal injection, the output signals of both sensors S3, S6 reach a plateau during the maximum flow rate of the radiopharmaceutical. The system controller 9000 may monitor the output signal of the sensor S6 at a predetermined time, for example, at time T9, for signs of extravasation. In particular, the system controller 9000 may compare the output signal of the sensor S6 at time T9 with the output signal of the sensor S6 at time T4. If there is a retention at time T4, the system controller 9000 may record the rate of increase of the output signal of the sensor S6 and consider it to correspond to a retention. Thus, if the output signal of the sensor S6 increases at time T9, the system controller 9000 may compare the rate of increase at time T9 to the learned rate of increase at time T4. If the increase in the output signal of the sensor S6 at time T9 is similar or equal to the increase at time T4, the system controller 9000 may determine that a previous retention has occurred at T9 and may alert the operator and continue the infusion. Conversely, if the increase in the output signal of the sensor S6 at time T9 is more rapid than the increase at time T4, the system controller 9000 may determine that extravasation has occurred at time T9. In some embodiments, the system controller 9000 may use a threshold based on the output signal at time T4 to distinguish between retention and extravasation at time T9. For example, the system controller 9000 may determine that extravasation has occurred at time T9 if the rate of increase of the output signal of sensor S6 at time T9 exceeds the rate of increase of the output signal at time T4 by a predetermined percentage.

[0281] If the system controller 9000 determines that extravasation is occurring at time T9 or any time thereafter, the system controller 9000 may pause, hold, or stop the injection and alert the operator until further action can be determined. If the rate of increase in the output signal of sensor S6 at time T9 is similar to or less than the rate of increase in the output signal at time T4, the system controller 9000 may proceed to terminate the injection procedure.

[0282] An alternative method of monitoring the system 1000 for extravasation using sensor S6 can also be seen from Figs. 52 and 53. Instead of splitting the radiopharmaceutical injection into multiple predetermined volumes separated by flushes, as previously described, the system controller 9000 may intend to deliver the entire volume of the radiopharmaceutical in a single dose. As with the previous embodiment, the output signal of sensor S6 is expected to reach a plateau at time T4 during normal operation (i.e., no retention or extravasation is present). As long as the output signal of sensor S6 remains at the plateau as expected, the system controller 9000 proceeds to inject the entire dose of the radiopharmaceutical in a single step (similar to the time curve shown in Fig. 49). However, an increase in the output signal of sensor S6 after time T4 indicates that the radiopharmaceutical is not flowing through the patient's vasculature as intended. To distinguish between extravasation and retention (i.e., slow clearance), the system controller 9000 may pause the injection of the pharmaceutical and continue to inject only the flushing agent. At time T5, the system controller 9000 observes whether the output signal of sensor S6 has plateaued or is decreasing. If the output signal of sensor S6 remains at the plateau at time T5, or if the output signal has not decreased by a predetermined magnitude, percentage, etc., the system controller 9000 alerts the operator to possible extravasation and stops the injection. In contrast, if the output signal of sensor S6 has decreased by a predetermined magnitude, percentage, etc., at time T5, the system controller 9000 may determine that retention, rather than extravasation, is occurring. The system controller 9000 may then resume normal injection of the radiopharmaceutical and use the rate of rise of the output signal of sensor S6 measured at T4 to evaluate whether the rise at T9 is within an expected range during the remainder of the injection, e.g., or whether extravasation (rises too fast) or leakage (rises too slow or lack of rise) may be occurring. If any malfunction is detected, the system controller 9000 may alert the operator and the system controller 9000 may pause the injection automatically or upon operator command.

[0283] FIG. 54 is another embodiment of the system 1000 that combines all of the features of the embodiments shown in FIGS. 40, 42, 43, 44, 45, 46, and 47. The embodiment of FIG. 54 includes a filter 3000 substantially as described in connection with FIG. 40, and a temporary fluid reservoir 1020C and associated components substantially as described in connection with FIGS. 42 and 43. The system 1000 may further include one or more auxiliary fluid pumps or reservoirs 1020D, 1020E for infusing additional fluids such as protective agents, uptake enhancers, amino acid mixtures, etc. Infusion from all fluid reservoirs 1020A-1020E is controlled by the system controller 9000, allowing the system 1000 to deliver several fluids in a controlled sequence. Fluids, such as radiopharmaceuticals, flushing agents, and any additional / auxiliary fluids, may be drawn from respective bulk fluid sources 1012A, 1012B, 1012D, 1012E into respective fluid reservoirs 1020A, 1020B, 1020D, 1020E. Implementations of such bulk fluid sources are described herein with reference to FIG. 44. System 1000 may include multi-patient to single-patient connectors at various locations, e.g., connector C1 and connector C1′, depending on which fluid path elements are designed to be multi-patient and which fluid path elements are designed to be single-patient.

[0284] Various valves V1-V10 are disposed throughout the fluid path set 1010 and are operated by the system controller 9000 to control the flow of one or more fluids through the various fluid path elements, fluid reservoirs 1020A, 1020B, 1020D, 1020E, and bulk fluid sources 1012A, 1012B, 1102D, 1012E. The valves V1-V10 may be active valves, such as pinch valves or stepper motor rotary actuated stopcocks, passive valves, such as stopcocks, or manually actuated valves.

[0285] One or more of the auxiliary fluid reservoirs, for example the auxiliary fluid reservoir 1020E shown in FIG. 54, may be fluidly connected to a second intravenous administration site 1019 on the patient that is different from the intravenous administration site 1018 where the radiopharmaceutical from the first fluid reservoir 1020A is injected. This may be done, for example, in cardiac stress imaging where a steady flow of stress agent from the fluid reservoir 1020E to the patient P must be maintained at a prescribed flow rate that should not be accelerated or decelerated by the injection of the radiopharmaceutical. In another example, the auxiliary fluid or drug from the auxiliary fluid reservoir 1020D or 1020E may be an amino acid mixture to reduce the dose to the kidney from radiotherapy. In another example, the auxiliary fluid reservoir 1020D or 1020E may be a "cold" version of a target molecule that does not have a radioisotope attached to it. Alternating "hot" and "cold" versions of the target molecule may be used in receptor binding studies or as described in U.S. Pat. No. 10,016,618.

[0286] 54, the system 1000 may include a reference radiation sensor S7 located on the patient P away from the intravenous administration site 1018. The sensor S7 may be on the patient's contralateral limb, on the liver, or on a target organ such as the heart or kidney. The system controller 9000 may be configured to compare an output signal of the reference radiation sensor S7, which would be indicative of whole body distributed radiation, with an output signal of the sensor S6 to identify the presence of retention or extravasation near the sensor S6.

[0287] 54, the system 1000 may include one or more waste containers 4000 to safely contain air from priming, radiopharmaceutical, or other fluids for disposal. The waste containers 4000 may be in fluid communication with the first fluid reservoir 1020A and the interim fluid reservoir 1020C such that if a faulty dose of radiopharmaceutical is detected, the system controller 9000 may redirect the faulty dose to the waste containers 4000 via valves V7, V9. The filled waste containers 4000 may then be safely removed from the system 1000 and discarded. The injection procedure may be resumed with a new dose of radiopharmaceutical.

[0288] As described herein, the system controller 9000 of any of the embodiments of the system 1000 illustrated in FIGS. 40-54 may perform an injection procedure to deliver any of the fluids from the various fluid reservoirs 1020A-1020E to the patient P. During delivery of the fluid, the system controller 9000 may be configured to receive output signals corresponding to radiation measurements from the sensors S1-S7. Based on these radiation measurements, the system controller 9000 may be configured to make various decisions and stop or modify the injection procedure. In some examples, as described herein, the system controller 9000 may be configured to determine that an amount of radioactive particles in any of the fluid path elements or fluid reservoirs 1020A-1020E meets a predetermined threshold. Examples of such predetermined thresholds include a predetermined prescribed dose of the radiopharmaceutical, a predetermined safe dose of the radiopharmaceutical, a predetermined dwell amount, and a predetermined rate of change of radioactivity over time.

[0289] In some examples, the system controller 9000 may be configured to determine a cumulative amount of radiopharmaceutical injected from the first fluid reservoir 1020A or the interim fluid reservoir 1020C. The system controller 9000 may make this determination based on radiation measurements from one or more of the sensors S1-S7 and one or more injection parameters. Exemplary injection parameters include the injection rate of the radiopharmaceutical, the injection volume of the radiopharmaceutical, the injection duration of the radiopharmaceutical, the half-life of the radiopharmaceutical, the decay series of the radiopharmaceutical, the age of the radiopharmaceutical, the volume of the radiopharmaceutical, the concentration of the radiopharmaceutical, and the initial activity of the radiopharmaceutical. During or after the injection, the system controller 9000 may compare the cumulative amount of the radiopharmaceutical injection to the prescribed dosage as a confirmation check. In some examples, the system controller 9000 may be configured to record, report to a user, or communicate to an external system any or all of the information related to the injection, including, for example, one or more injection parameters.

[0290] In some examples, the system controller 9000 may be configured to determine a remaining level of radioactive particles in the radiation filter 3000 or in the fluid path set 1010 based on the radioactivity measurements received from one of the sensors S3-S5. In some examples, the system controller 9000 may be configured to determine that a radiopharmaceutical is chelated based on the radioactivity measurements received from one or more of the sensors S1-S7. In some examples, the system controller 9000 may be configured to determine the amount of radioactive particles retained in the filter 3000 by comparing the radioactivity measurements from the sensors S3 and S5.

[0291] In some examples, the system controller 9000 may be configured to determine the presence of retention or extravasation associated with the intravenous administration site 1018 based on radiation measurements received from at least one of the sensors S3-S6. In particular, the system controller may obtain radiation measurements from sensor S3 in the fluid pathway set 1010 and sensor S6 at the intravenous administration site 1018. In some examples, the system controller 9000 may be configured to detect an occlusion or leak in the fluid pathway set 1010 based on radiation measurements received from at least one of the sensors S3-S6. In particular, the system controller 9000 may determine from a lack of radiation measurements at any of the sensors S3-S6 that the radiopharmaceutical is not reaching that sensor as intended, indicating a leak or occlusion. Additionally, a significant increase in the radiation measurements at any of the sensors S3-S5 in the fluid pathway set 1010 may indicate an accumulation of the radiopharmaceutical due to an occlusion.

[0292] It should be noted that the various embodiments of the system 1000 described herein are shown diagrammatically, with the various components positioned relative to one another to clearly illustrate the operation of the system 1000. However, the placement of components in an actual implementation may vary, and individual components may be stored in different rooms, or even in completely different locations. For example, the fluid reservoirs 1020A, 1020C, 1020D, 1020E containing radioactive materials may be stored in a room separate from the patient P to avoid unnecessary radiation exposure to the patient P and the operator. The system controller 9000 may include components such as a server and memory connected wired and / or wirelessly to at least one processor from a remote location. Additionally, the system controller 9000 may be connected to a wearable device, such as a smartphone, a smartwatch, and the like, and share information with the wearable device.

[0293] Although the various fluid reservoirs 1020A-1020E are generally described as syringe-piston-plunger devices, any form of fluid pump and reservoir may be used. For example, any of the fluid reservoirs 1020A-1020E may include a bottle, bag, syringe, or tube with a peristaltic pump for fluid delivery or a pressurized reservoir. Peristaltic, diaphragm, piston, etc. fluid pumps may be used. Generally, positive displacement pumps may be used, as well as non-positive displacement pumps combined with sufficiently accurate flow meters or volumetric flow meters. As discussed herein, the first fluid reservoir 1020A containing the radiopharmaceutical may alternatively be a generator for producing the radiopharmaceutical with the fluid driven or drawn through it.

[0294] The embodiments of the system 1000 described herein may be used to inject a wide variety of radiopharmaceuticals, the details of which are described in various patent documents incorporated by reference. Such radiopharmaceuticals may include, for example, various isotopes of technetium, thorium, actinium, radium, and rubidium. Depending on the isotope and injection procedure, the prescribed dosage may range from a fraction of a milliliter (mL) to tens of milliliters, for example, about 7 mL.

[0295] In view of the above, the various fluid delivery systems of the present disclosure are capable of improved methods of treating various medical problems, particularly for methods and systems for radiation therapy delivery where radiation therapy is set to expand by up to about 10-fold in the near future. Given this potential increase in the need for radiation therapy to treat various medical conditions, there is a need to expand the locations and people where radiopharmaceuticals can be administered and / or administered. Furthermore, the fluid delivery systems of the present disclosure may be designed to (i) reduce radiation exposure received by the operator / administrator, (ii) provide the operator / administrator with better awareness of the dose and / or dose rate of the radiopharmaceutical given to a particular patient, and / or (iii) provide one or more separate filters, one or more separate sensors, and / or one or more separate controllers so that the fluid delivery systems of the present disclosure can handle any isotope-based radiopharmaceutical. Furthermore, the fluid delivery systems of the present disclosure may be designed to reduce connections to be made and reduce, eliminate, or prevent disconnections to be made after the procedure is completed to reduce the possibility of leakage or transfer of hazardous materials to the operator or the environment.

[0296] In addition, various fluid delivery systems of the present disclosure may provide embodiments that may eliminate dose calibrators, as dose calibrators may be expensive and / or cumbersome to maintain. Thus, in one example, various fluid delivery systems of the present disclosure may function with multiple syringes of various volumes from 5 mL to 65 mL. In another example, various fluid delivery systems of the present disclosure may provide embodiments that allow an operator / administrator to (i) deliver cytoprotective and other preparatory drugs, (ii) deliver sensitizing drugs, (iii) pause and resume an injection mid-procedure without losing information and / or accuracy (e.g., pausing to flush various lines before opening), and / or (iv) detect one or more leaks.

[0297] In yet another example, the various fluid delivery systems of the present disclosure allow an operator / administrator to achieve a customized dose for a patient based on one or more factors including, but not limited to, body weight, infusion rate, total volume, and / or select a desired flow rate depending on one or more patient conditions and / or factors (e.g., proteins require slower infusion), and / or the ability to provide more or less saline to a patient depending on individual patient requirements and / or various treatment requirements.

[0298] In yet another example, the various fluid delivery systems of the present disclosure enable an operator / administrator to administer a wide range of other types of drugs other than radiopharmaceuticals, including, but not limited to, one or more imaging drugs (e.g., CT contrast, MR contrast, ultrasound contrast, etc.), chemotherapy drugs, immunomodulatory drugs (e.g., drugs for one or more autoimmune disorders including, but not limited to, controlling Crohn's disease, ulcerative colitis, rheumatoid arthritis, lupus, multiple sclerosis, etc.) In yet another example, the various fluid delivery systems of the present disclosure may be used to deliver (i) Sirtex® spheres for the treatment of solid tumors, etc., and / or (ii) pre-loaded, single-use patient doses.

[0299] In yet another example, the various fluid delivery systems of the present disclosure allow for the use of any electronically readable sensor, including but not limited to electronic dosimeters, Lucerno® devices, ionization chambers, scintillators with photodiodes or avalanche photodiodes, etc. In yet another example, the various fluid delivery systems of the present disclosure allow for real-time or other radiation sensing of alpha, beta direct, beta bremsstrahlung (e.g., decelerated radiation or bremsstrahlung), gamma, and / or neutrons. In yet another example, the various fluid delivery systems of the present disclosure utilize various radiation sensing modes via various methods and / or devices, including but not limited to pulse counting, current, pulse height (charge) measurement, Geiger counters, solid-state pulse counters (CZT), diode current measurement, suitable types of gamma ray spectrometers, Lucerno® extravasation detectors, ThermoFischer Scientific® sensors, Berkley® nuclear technology sensors, and / or RFID radiation sensors.

[0300] Referring now to FIG. 55, FIG. 55 illustrates a remote cockpit device that provides remote access to and / or by an off-site or remote operator OP2, which may be an experienced and / or licensed personnel, such as, for example, a nuclear medicine technician or physician, radiation oncologist, health physicist, or authorized user, to enable the remote personnel to oversee, control, or otherwise legally perform drug preparation and delivery to meet local legal and / or regulatory requirements. The off-site may be some distance away, including another room in the same facility or campus, or another location in the same state, same country, or another country. This has the advantage of allowing more sites and more operators to deliver drugs, thus expanding patient access to the drug. To enable this remote cockpit capability, additional systems 9050 communicate with the system controller 9000. The off-site system may have an off-site controller and a user interface. The off-site controller may be, for example, a laptop computer with sufficient software to allow the off-site operator to observe and / or perform all functions that can be performed via the on-site user interface 9010, preferably including checking the status of all aspects of the drug delivery system 100 and / or the fluid injection system 1000. Capabilities such as these are commonly used in IT services for many organizations because they give remote IT professionals full access to local computers. One important feature that the off-site operator can use to great advantage is the ability to speak face-to-face with the on-site operator. Capabilities such as these are available through a variety of systems, including but not limited to Microsoft Teams®, Zoom®, and other systems. Another important feature that the off-site operator can use to great advantage is the ability to communicate with the patient as if the patient was in the room.Another important feature that the off-site operator can use to great advantage is the ability to control and / or use the system camera 117 to visualize what is happening on-site and in the laboratory, preferably including visually observing the status of all aspects of the drug delivery system 100 and / or fluid injection system 1000. It is desirable for the off-site operator to be able to move and zoom the camera 117 as he feels is most useful. The camera 117 may also be head mounted or worn by the on-site operator OP1 so that what the on-site operator OP1 sees is exactly what the off-site operator OP2 sees. At the most basic level, the remote operator OP2 need only respond to requests for advice or assistance from the on-site operator OP1. At the most complete level, the remote operator OP2 may be responsible for the entire operation, with the on-site operator OP1 performing activities as directed by the remote operator OP2 and under the supervision of the off-site operator. Intermediate levels of interaction and control may be used as needed based on the expertise of the on-site operator OP1 and legal regulations.

[0301] In one embodiment, the remote system 9050 comprises an off-site controller 9052, a user interface 9060, and additional systems 9080 that can be controlled by a remote operator OP2 as described herein. The controller 9052, interface 9060, and additional systems 9080 can be the same or different as those located on-site, and are formed from any of the possibilities described above with respect to the similarly labeled on-site components of 9000, 9010, 9030, and OP1. Further embodiments of the present disclosure may utilize various remote or virtual cockpits as disclosed and described in detail in U.S. Provisional Patent Application No. 63 / 336,512, filed April 29, 2022, the disclosure of which is incorporated herein by reference in its entirety.

[0302] Although the embodiments or aspects have been described in detail for purposes of illustration and explanation, it should be understood that such details are for that purpose only, and that the embodiments or aspects are not limited to the disclosed embodiments or aspects, but on the contrary are intended to cover modifications and equivalent arrangements within the spirit and scope of the appended claims. Various methods of operating the various systems of the present disclosure are described through one or more exemplary embodiments. These methods of operation are applicable to all embodiments that provide sufficient components for such operation. In some embodiments, there may be more components or elements than are required to perform a particular method. The embodiments of the present disclosure may be simplified based on the functionality to be supported or required in a particular situation. For example, it should be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment or aspect may be combined with one or more features of any other embodiment or aspect. Indeed, many of these features may be combined in ways not specifically recited in the claims and / or disclosed herein. Although each dependent claim set forth in the claims may depend directly on only one claim, the disclosure of possible implementations includes the combination of each dependent claim with all other claims in the claim set. [Explanation of symbols]

[0303] 100 delivery system, delivery device, 100' delivery system, 102 mobile cart, 102' stationary cart, 104 wheels, 106 storage component, storage compartment, 106' storage component, 108 first drawer or shelf, storage compartment, 110 second drawer or shelf, 112 third drawer or shelf, container compartment, 113 compartment for storing auxiliary equipment, auxiliary equipment compartment, 114 controller, 114' controller, 116 user display, 116' user display, 117 camera, 118 input device, 119 output device, printer, 120 lock, 122 wheel lock, 124 mobile base, 150 assembly, 170 injector, 170' injector, 172 access mechanism, 174 delivery mechanism, 176 alignment pin, 178 valve assembly, 180 air detector, 182 Probe, 184 Spike driver, 186 Plunger driver, 190 Disinfection mechanism, 192 Movable arm, 194 Disinfection source, 200 Storage device, storage container, 200' Storage device, storage container, 201 Housing, 201' Housing, 202 Chamber, 202' Chamber, 204 Body, 204' Body, 206 Proximal end, 206' Proximal end, 208 First opening, 208' First opening, 210 Distal end, 210' Distal end, 212 Second opening, 214 Cap, 216 One or more clips, 217 Gasket or seal, 218 Inner portion, 220 Outer portion, 222 One or more connectors, 224 Cavity, 226 Receptacle, 226' Receptacle, 228 Therapeutic or diagnostic agent, agent, 230 Proximal end, 232 access port, 232' access port, 234 distal end, 234' distal end, 236 interior, 238 ribs, 240 holder, 242 contact element, 244 tabs, 246 interior surface, 248 door, 250 access opening, 252 door cover, 252' door cover, 254 door access opening, 254' access opening, 256 seal, 258 container access opening, 260 door lock, 262 at least one first hook, 264 at least one second hook, 266 angled contact surface, 268 catch, 270 label or tag, 272 guide mechanism, 274at least one identification feature, 276; proximal cap, 278; retainer, 280; base, 282; retaining portion, 284; inner surface, 286; outer surface, 288; threaded collar, 290; cover, 292; threads, 294; distal end, 296; inner engagement surface, 298; seal, 300; fluid cassette, 300'; fluid cassette, 302; enclosure, housing, 302'; enclosure, 304; first portion, 306; second portion, 308; interior, 310; spike, 312; syringe, 314; fluid path set, 315; spike opening, 316; valve block, 317; particle / air filter, air / particle filter, 320; body, 322; proximal end, 324; distal end, 326; at least one piercing tip, 328; fluid path connector, 329 filtered vent, 330 collar, 332 absorbent material, 334 drive element, 336 spike drive slot, 337 alignment element, 338 barrel, 340 proximal end, 342 distal end, 344 internal chamber, 346 plunger, 350 port, 352 plunger opening, 354 flange, 356 flange slot, 358 plunger cap, 362 at least one first hook, 364 at least one second hook, 366 angled contact surface, 368 catch, 370 alignment element, 376 plunger drive receiver, 378 recess, 380 guiding feature, 382 locking element, 384 first valve, 388 first port, 390 second port, 392 third port, 394 auxiliary fluid source, 395 spike, 396 Auxiliary line, 397, check valve, 398, auxiliary branch, 399, pair of connectors, 400, second valve, 402, third valve, 403, air / particulate filter, 404, end connector, 406, infusion set, 408, proximal connector, 410, distal connector, 412, catheter, 414, priming cap, 416, pair of check valves, 418, occlusion detection sensor, 420, air detector, 450, storage container, 452, housing, 454, interior, 456, storage portion, 458, lid portion, 460, hinge, 462, waste container, 464, housing, 466, interior, 474, label, 476, waste locker, 478, drawer or shelf, 480, indicator, 482, inventory computer, 484, door, 486Locking mechanism, 1000 fluid injection system, 1010 fluid path set, 1012 connection, 1012A bulk supply, 1012B bulk supply, 1012D bulk supply, 1012E bulk supply, 1014 valve, 1016 catheter, 1018 intravenous administration site, 1019 second intravenous administration site, 1020A fluid reservoir, 1020B fluid reservoir, 1020C interim pump or fluid reservoir, 1020D auxiliary pump, 1020E auxiliary 2 pump, 1030A plunger, 1030B plunger, 1030C plunger, 1030D plunger, 1030E plunger, 1040 piston actuator, 2000 fluid delivery graph, 2020 shield, 2020' radiation shield', 2100 graph of fluid infusion over time, 2200 graph of sensor output signal, 2220 radiation shield, 2300 graph of fluid infusion over time, 2400 graph of sensor response over time, 2500 graph, 2600 graph, 3000 filter, 4000 waste, 9000 system controller, 9010 user interface, 9030 additional system, 9030 auxiliary system, 9050 additional system, 9052 offsite controller, 9060 user interface, 9080 additional system, C1 connector, D1 data element, D1' data element, D2 data element, OP1 onsite operator, OP2 offsite / remote operator, P patient, S1 sensor, S1' sensor, S2 sensor, S2' sensor, S3 sensor, S4 sensor, S5 sensor, S6 sensor, S7 sensor

Claims

1. 1. A fluid injection delivery system comprising: at least one fluid reservoir comprising a first fluid reservoir configured to receive a radiopharmaceutical; a radiation filter in fluid communication with the at least one fluid reservoir, the radiation filter configured to retain radioactive particles from the radiopharmaceutical that pass through the radiation filter; at least one sensor configured to detect and measure radioactivity in at least one of the first fluid reservoir, the radiation filter, and a set of fluid paths in fluid communication with the radiation filter; A controller in operative communication with the at least one sensor, the controller comprising: receiving radioactivity measurements from the at least one sensor; determining, based on the radioactivity measurements, that an amount of radioactive particles in at least one of the first fluid reservoir, the radiation filter, and the fluid path set meets a predetermined threshold; The controller and A fluid injection delivery system comprising:

2. The predetermined threshold value is a predetermined prescribed dosage of said radiopharmaceutical; a predetermined safe dosage of said radiopharmaceutical; The predetermined retention amount, a predetermined rate of change of radioactivity with respect to the volume of fluid displaced through said filter; and A given rate of change in radioactivity over time The fluid injection delivery system of claim 1 , comprising at least one of:

3. 10. The fluid injection delivery system of claim 1, wherein the controller is further programmed or configured to determine a cumulative amount of the radiopharmaceutical injected from the first fluid reservoir based on the radioactivity measurements and one or more injection parameters.

4. The one or more injection parameters include: an injection rate of said radiopharmaceutical; an injection volume of said radiopharmaceutical; duration of injection of said radiopharmaceutical; the half-life of said radiopharmaceutical; the decay series of said radiopharmaceutical; the age of said radiopharmaceutical; a total volume of said radiopharmaceutical; the concentration of said radiopharmaceutical; and Initial activity of the radiopharmaceutical The fluid injection delivery system of claim 3 , comprising at least one of:

5. 4. The fluid injection delivery system of claim 3, wherein the controller is further programmed or configured to compare the cumulative amount of the injected radiopharmaceutical with a predetermined prescribed dosage.

6. 4. The fluid injection delivery system of claim 3, wherein the controller is further programmed or configured to adjust an injection rate of the radiopharmaceutical based on the cumulative amount of the radiopharmaceutical injected.

7. 4. The fluid injection delivery system of claim 3, wherein the controller is further programmed or configured to stop an injection procedure in response to the cumulative amount of the radiopharmaceutical injected meeting the predetermined threshold.

8. 10. The fluid injection delivery system of claim 1, wherein the controller is further programmed or configured to determine a residual level of radioactive particles within the radiation filter or the fluid pathway set based on the radioactivity measurements received from the at least one sensor.

9. The fluid injection delivery system of claim 1 , wherein the controller is further programmed or configured to determine that the radiopharmaceutical is chelated based on the radioactivity measurements received from the at least one sensor.

10. The at least one sensor is a first sensor associated with a fluid path set upstream of the radiation filter; a second sensor associated with a fluid path set downstream of the radiation filter; and Equipped with the controller is programmed or configured to determine the amount of radioactive particles retained by the radiation filter by comparing a radioactivity measurement from the first sensor with a radioactivity measurement from the second sensor. The fluid injection delivery system of claim 1 .

11. 2. The fluid injection delivery system of claim 1, wherein the fluid pathway set comprises an intermediate container in fluid communication with and located downstream of the at least one fluid reservoir, at least one of the at least one sensor is associated with the intermediate container to detect radioactivity in the intermediate container, and the controller is configured to prevent delivery of the radiopharmaceutical from the intermediate container to a patient based on the amount of radioactive particles in the intermediate container deviating from the predetermined threshold.

12. The fluid injection delivery system of claim 1 , wherein the at least one fluid reservoir further comprises an additional fluid reservoir configured to inject a flushing agent.

13. 10. The fluid injection delivery system of claim 1, wherein the at least one fluid reservoir further comprises an additional fluid reservoir configured to inject a second medication.

14. 14. The fluid injection delivery system of claim 13, wherein the second pharmaceutical agent is a protectant.

15. The fluid injection delivery system of claim 1 , wherein the first fluid reservoir comprises a radiopharmaceutical generator.

16. The first fluid reservoir comprises: a housing having a chamber defined therein; a container disposed within the chamber, the container having an interior therebetween, the container having a distal end opposite a proximal end configured to receive a radiopharmaceutical, the proximal end having an access port for accessing the interior; a door associated with the housing, the door being movable relative to the housing between a closed position and an open position, in the closed position the door covers an opening in the housing to enclose the chamber of the housing, and in the open position the door exposes the opening in the housing for accessing the access port of the container; a holder within the chamber of the housing for contacting the container to secure the container relative to the housing such that the access port of the container is located at the opening of the housing; Equipped with the door is movable between the closed position and the open position in response to actuation by an access mechanism of the fluid injection delivery system. The fluid injection delivery system of claim 1 .

17. 1. A filtration system for a radiopharmaceutical fluid injection system, the filtration system comprising: a radiation filter in fluid communication with at least one fluid reservoir of the radiopharmaceutical fluid injection system, the radiation filter configured to retain radioactive particles from a radiopharmaceutical received from the radiopharmaceutical fluid injection system; at least one sensor configured to detect and measure radioactivity in at least one of the fluid reservoir, the radiation filter, and a set of fluid paths in fluid communication with the radiation filter; A controller in operative communication with the at least one sensor, the controller comprising: receiving radioactivity measurements from the at least one sensor; determining whether an amount of radioactive particles in at least one of the fluid reservoir, the radiation filter, and the fluid path set meets a predetermined threshold based on the radioactivity measurements; The controller and A filtration system comprising:

18. 1. A fluid injection system comprising: at least one fluid reservoir comprising a first fluid reservoir configured to inject a radiopharmaceutical; a fluid path set in communication with the at least one fluid reservoir, the fluid path set comprising one or more fluid path elements including a fluid path set sensor and a catheter configured for insertion into an intravenous administration site of a patient; a patient sensor configured to detect and measure radioactivity in a patient associated with the intravenous administration site; A controller in operative communication with the patient sensor and the fluid pathway set, the controller comprising: receiving a radioactivity measurement from the patient sensor; determining whether or not the radiopharmaceutical has been retained in the patient based on the radioactivity measurements from the patient sensor; The controller and A fluid injection system comprising:

19. The fluid injection system of claim 18, wherein the fluid pathway set sensor is configured to detect and measure radioactivity within a portion of the fluid pathway set upstream of the intravenous administration site.

20. 20. The fluid injection system of claim 18, wherein the controller is further programmed or configured to modify or stop an injection procedure in response to determining the presence of retention of the radiopharmaceutical in the patient.

21. 20. The fluid injection system of claim 19, wherein the controller is further programmed or configured to determine the presence or absence of retention of the radiopharmaceutical associated with the intravenous administration site based on the radioactivity measurements from the patient sensor and the fluid pathway set sensor.

22. 22. The fluid injection system of claim 21, wherein the at least one fluid reservoir further comprises a second fluid reservoir configured to inject a flushing agent, and the controller is programmed or configured to increase the injection of the flushing agent in response to determining retention of the radiopharmaceutical at the intravenous administration site.

23. 20. The fluid injection system of claim 19, wherein the controller is further programmed or configured to determine a leak in the fluid pathway set based on a comparison of the radioactivity measurements from the patient sensor and the fluid pathway set sensor.

24. 20. The fluid injection system of claim 19, wherein the controller is further programmed or configured to determine an occlusion in the fluid pathway set based on a comparison of the radioactivity measurements from the patient sensor and the fluid pathway set sensor.

25. and an interrogation sensor configured to detect and measure radioactivity in the patient remote from the intravenous administration site, the controller further comprising: receiving a radioactivity measurement from the interrogation sensor; determining the presence or absence of retention of the radiopharmaceutical in the patient based on a comparison of the radioactivity measurements from the patient sensor and the interrogation sensor; 20. The fluid injection system of claim 18, programmed or configured to:

26. 1. A retention detection system for a radiopharmaceutical fluid injection system, the retention detection system comprising: a patient sensor configured to detect and measure radioactivity in a patient proximate an intravenous administration site on said patient; a fluid path set sensor configured to detect and measure radioactivity in a fluid path set of the fluid injection system upstream of the intravenous administration site; a controller in operative communication with the patient sensors and the fluid pathway set sensors, the controller comprising: receiving radioactivity measurements from the patient sensor and the fluid pathway set sensor; determining whether or not the radiopharmaceutical is retained in the patient based on the radioactivity measurements from the patient sensor and the fluid pathway set sensor; The controller and A retention detection system comprising:

Images