Mobile automated device for preparing and administering a radiopharmaceutical dose to a patient and methods for implementing the automated device

Abstract

The present invention relates to a mobile apparatus (1) for the automatic on-demand preparation and injection or infusion of a dose of radiopharmaceutical product to a plurality of patients, in which a kit (32, 100) comprises a controlled syringe (101) for withdrawing the radiopharmaceutical product after piercing, by means of a motorized system, a septum of the radiopharmaceutical product vial (31, 107), and a three-way valve (103) which successively allows the radiopharmaceutical product to be withdrawn into the syringe (101), mixed with a quantity of saline (33, 109), and injected into a patient via three respective fluid paths (106, 108, 241 and optionally 242).

Description

MOBILE AUTOMATED UNIT FOR PREPARING AND ADMINISTERING A RADIOPHARMACEUTICAL DOSE TO A PATIENT AND METHODS FOR IMPLEMENTING THE AUTOMATED UNIT Scope of the invention

[0001] The present invention relates to a mobile automated system designed to prepare and administer (i.e., in particular, inject / infuse) doses of radiopharmaceuticals to patients. The invention also relates to one or more methods for implementing the device.

[0002] More specifically, the invention relates to a mobile automated system for preparing and injecting positron emission tomography (PET) tracers into patients from a multi-dose vial, ensuring radiation protection for hospital staff and traceability of all operations. Technological background

[0003] Primarily used in medical imaging or nuclear medicine, radiopharmaceuticals must be precisely dosed before administration to a patient while minimizing healthcare personnel's exposure to ionizing radiation.

[0004] Currently, it is known that administering a radioactive product to a patient ideally requires easy-to-use, largely automated, and mobile devices.

[0005] A mobile injection device designed to administer radiopharmaceuticals in a clinical setting must therefore meet a number of essential specifications.

[0006] First, it must be compact and lightweight, which facilitates its maneuverability within the hospital. Ideally, it should be mounted on wheels, motorized or not.

[0007] In addition, the dose preparation and administration mechanism must allow for the preparation / injection of precise doses with controlled speed and injection volume.

[0008] More specifically, the preparation involves drawing the specific dose for a given patient from a multidose vial, with each patient dose being precisely drawn and measured. The injection consists of injecting the drawn and isolated dose into a patient vein using a syringe from a kit with regulated flow and pressure. Ideally, the device also allows for a secondary use: injecting the prepared dose into an external shielded syringe, for example, placed on the injector's tray, for subsequent manual administration to the patient. The required radiation protection consists of protecting users from ionizing radiation emitted by the multidose solution in the vial and carried through the system's tubing.Finally, traceability consists of retrieving, in an automated, semi-automated or user-encoded manner, data such as the dose injected into the patient, patient data, consumable references (by reading RF-tag, batch number, volumes, ...), etc.

[0009] The device and its consumables must be compatible with a wide range of radiopharmaceuticals commonly used in diagnostic and therapeutic procedures, including the ability to handle different formulations and concentrations.

[0010] Furthermore, radiation protection is paramount to safeguard operators, nursing staff, and patients from any avoidable exposure and to keep it well below regulatory limits, even under intensive use. Safety features, such as interlocks and a stop button that instantly cuts off the power supply to the syringe pump, are integrated to prevent or interrupt accidental injection or exposure.

[0011] The control interface must be easily understandable for the operator and include a touch screen or keyboard for entering information relating to the patient, tests and other protocols to be performed, as well as a clear display of the instantaneous status of the current injection and alerts.

[0012] Ideally, two power sources ensure uninterrupted operation, even in the event of a power outage or when the device is being moved: first, a DC source, in the form of a battery, which is the primary power source for the device, and second, an AC source, in the form of a mains connection, used when the battery is low and for recharging. This solution allows for uninterrupted use of the device.

[0013] Connectivity options with hospital networks, including Wi-Fi, Bluetooth and / or USB ports, are provided for data transfer both in routine operation and for updates to integrate any future developments in the device's features.

[0014] These features are particularly related to traceability and ease of use, especially regarding the patient list, which is often imported from dedicated hospital software. The injector can interface with this software to easily retrieve the patient list and a range of information, such as the dose to prepare and administer throughout the day. Communication also works in both directions. For example, once the dose has been injected into the patient, the device allows the injection data to be shared with the hospital's management software.

[0015] Remote monitoring and diagnostic capabilities will advantageously allow healthcare professionals to supervise operations and manage troubleshooting or maintenance issues remotely.

[0016] Easy cleaning and maintenance features, such as easily cleanable surfaces and accessible components, promote the maintenance of healthy operating conditions that minimize bacteriological risks in the hospital environment.

[0017] The device and its consumables comply with the performance, safety and usage objectives defined in the standards and regulations to which users are subject.

[0018] The system must be able to record data collected as it is used and generate reports for the purposes of verifying operations carried out, compliance, auditing and quality assurance. State of the art

[0019] US patent 9,114,203 B2 discloses shielding assemblies for systems that generate and infuse radiopharmaceuticals. The shielding assemblies include a sidewall that defines multiple compartments and provides a radiation barrier for those compartments, as well as a communication line to a radioisotope generator incorporated in the first compartment. A second compartment is intended to house part of an infusion circuit, which may be an extension of the generator's eluate line and may include a waste line and a patient extension line.

[0020] In US 2010 / 312039 A1, from the same applicant, the configurations and assemblies of the infusion systems facilitate the routing of the infusion circuit tubing. The tubing is routed inside and outside the compartments of a shielding assembly for the infusion system, at locations that prevent kinking and / or crushing of the lines, and / or facilitate circuit assembly. Multiple lines can be held together by a support frame to form a disposable infusion circuit subassembly, which can further facilitate line routing.

[0021] An improvement of this device is disclosed in US 12,170,153 B2, with an integrated isotope generator equipped with a gamma detector and a beta detector for the detection of radioisotopes and contaminants (the apparatus and fluid path are identical).

[0022] US patent 9,607,722 B2 discloses methods for setting up, maintaining, and operating a radiopharmaceutical perfusion system, which includes a radioisotope generator, and whose operation is facilitated by a system computer. The computer includes pre-programmed instructions and a computer interface for interacting with a system user, for example, to monitor the volumes containing the eluent and / or eluate, and / or to monitor the time elapsed since the completion of an elution performed by the system, and / or to calculate one or more system and / or injection parameters for quality control, and / or to perform system purges, and / or to facilitate diagnostic imaging.

[0023] US Patent 9,750,953 B2 discloses systems and methods for administering a medical fluid. The system includes a fluid flow path, a fluid delivery device adapted to provide the medical fluid through the fluid flow path, and a controller communicating with the fluid delivery device. The method involves using the system to determine a desired flow rate of the medical fluid at a distal end of the fluid flow path based on at least one desired flow profile of the medical fluid at the distal end. The method also involves initiating a fluid delivery operation by providing the medical fluid through the flow path according to the fluid delivery parameters provided to the fluid delivery device by the controller.The controller can receive information about the fluid administration operation and perform a control function to adjust the fluid administration parameters based on the information received.

[0024] US patent 6,870,175 B2 discloses a method and apparatus for dispensing a radiopharmaceutical product in which: a source of flushing fluid is connected to a first port of a fluid dispensing assembly; a pressurization unit of a motorized injector system (comprising a motorized injector and the pressurization unit) is connected to a second port of the fluid dispensing assembly; air is purged from the fluid dispensing assembly; and, after purging the air from the fluid dispensing assembly, a third port of the fluid dispensing assembly is connected to a source of radiopharmaceutical product. A valve system is included to control the fluid flow. A syringe is connected to a motorized injector. A radioactive shield surrounds the syringe during operation to protect personnel from the adverse effects of the product. A dose calibrator measures the radioactivity in the syringe.

[0025] US patent 9,627,097 B2 discloses systems, apparatus, and methods by which an injection system automates the process of injecting a single dose from a multidose vial of a radiotracer. In some cases, the injection system includes a first dose calibration system that receives a multidose vial of radiotracer, a second dose calibration system, an injection pump, and an intravenous needle. In some cases, the first dose calibration system and the multidose vial are integrated. In some embodiments, the first dose calibration system includes a pneumatic arm that receives the multidose vial.

[0026] Document WO 2024 / 061619 A1 discloses a device for the reversible coupling of a syringe to an actuator, comprising an internal body with a longitudinal axis and an external sleeve capable of moving relative to the internal body along the longitudinal axis, the internal body comprising a sliding axis ending in a play-recovery plate held longitudinally inside the internal body in a rest position by a pre-loaded spring, and at least one pair of hooks arranged longitudinally inside the internal body, mounted pivotally and retractably in pairs about two respective axes perpendicular to the longitudinal axis, an external part of the hooks being located opposite an internal part of the sleeve, characterized in that the hooks of the same pair each have a hooking area at a proximal end of the play-recovery plate and are connected to each other at a distal end by a return spring,the distal part of the hooks being provided, on the outside, with a boss adapted to fit into a hollow area of ​​a first depth of the internal profile of the sleeve in a rest position of the coupling device where the hook engagement area is in the locking contact position of the push button, the hooks being brought together, the relative sliding of the sleeve with respect to the internal body, in which the sleeve moves away from said distal end of the hooks, causing the hooks to open by pivoting around their respective pivot axes, due to the boss of each hook entering a hollow area of ​​a second depth of the internal profile of the sleeve, the hollow area of ​​a second depth being adjacent to the hollow area of ​​a first depth, the first depth being greater than the second depth.

[0027] Document JP 2008253409 A discloses a complex radiopharmaceutical dosing device for dispensing radiopharmaceuticals by extracting them from a vial with a syringe, measuring the radiation dose with a detection sensor after extraction, and injecting physiological saline into the channel from a saline syringe when the radiopharmaceuticals are dispensed from the drug syringe. The syringes and vials are arranged on a vertical plane or in a vertical position. This arrangement ensures that the entire device is, in effect, in a vertical position, thus greatly limiting bubble formation in the internal channel.

[0028] US patent 2008 / 177126 A1 discloses a fluidic circuit for a fluid delivery system that includes a coiled tube designed to position one or more volumes of a pharmaceutical product within an ionization chamber for metering and preparing a pharmaceutical dose for administration to a patient. The tubular coil can be maintained in a desired dimensional geometry by means of a central structure around which the tubular coil is positioned.

[0029] Document AU 2023221939 A1 discloses a fluid injection system that includes at least one fluid reservoir configured to inject a radiopharmaceutical and a radiation filter in fluidic communication with the fluid reservoir(s). The radiation filter is configured to retain radioactive particles from the radiopharmaceutical that pass through it. The system further includes at least one sensor configured to detect radioactivity in at least one of the following: the fluid reservoir, the radiation filter, and a fluid path element in fluidic communication with the radiation filter; and a controller in operational communication with at least one sensor.The controller is programmed or configured to receive a radioactivity measurement from at least one sensor and determine, based on this measurement, that a quantity of radioactive particles in at least one of the following elements: the fluid tank, the radiation filter and the fluid circuit, meets a predetermined threshold. Objectives of the invention

[0030] The present invention aims at the development of a mobile and highly automated injector for the preparation and injection or infusion of radiopharmaceutical products directly to patients.

[0031] The present invention aims to implement at least part of the specifications stated above while solving the problems of the prior art, for example the choice of characteristics (choice of activity meter, positioning of the constant source, sampling characteristic, etc.) allowing the obtaining of a light, robust and ergonomic system and allowing extremely precise dose sampling, compared with the prior art.

[0032] In particular, the invention aims, within the framework of the automation of this device, to provide a capacity for correctly filling the lines of the kit and therefore indirectly for detecting a saline bag.

[0033] In particular, it aims to provide equipment and consumables, together enabling the safe collection, measurement and administration of a prescribed dose to multiple patients over a day.

[0034] In general, the present invention aims to multiply as many devices as possible that allow for increased automation, such as automatic bottle piercing, scanning of patient data and barcodes on bottles and saline bags, etc. of the invention

[0035] A first aspect of the present invention relates to a mobile device for the automatic on-demand preparation and intravenous administration of a dose of radiopharmaceutical product to a plurality of patients, comprising a plurality of compartments that are at least partially shielded: - a first compartment to accommodate a tubing kit allowing for the precise preparation, via several fluid paths, of a dose of radiopharmaceutical product diluted or not with a diluting agent such as saline, and for its direct injection into a patient; - a second compartment to hold a multidose vial of radiopharmaceutical product; as well as a space to accommodate a saline container and the connection to a patient extension tube; said kit, said saline container, and said multidose vial of radiopharmaceutical product being consumables configured to be replaced after treatment of one or more patients; said kit comprising a syringe intended to be controlled to dose and move fluids and a single three-way valve, cooperating with two non-return valves, which allows successively the radiopharmaceutical product to be withdrawn into the syringe, via a first tube ending with a needle intended for piercing a septum of a vial containing the radiopharmaceutical product, the radiopharmaceutical product to be aspirated and mixed with a quantity of saline conveyed by a second tube and the injection into a patient by a third tube; as well as : - means for preparing and administering fluid comprising a precision actuator for the syringe to be controlled and an actuator for the three-way valve; - an activity meter located near the syringe to be controlled to validate before injection a dose prepared using said kit; - a control system capable of communicating with the means for preparing and administering fluid, configured to receive dose preparation information for a patient from a user and to communicate corresponding instructions to the means for preparing and administering fluid; - a communication interface between said controller and a user, allowing the latter, via a menu of instructions, to launch a dose preparation and injection procedure, tests, calibrations, and access data in memory, for example, relating to the history of dose injections; and - means of storing and printing data.

[0036] According to the invention, the multidose vial is a shielded vial containing a plurality of tracer doses prepared outside the device and inserted into the device with its original shielding (a shielding adapter being optionally used); and the device includes at least one reference or constancy source in a shielded housing configured to control the activity meter, said source being able to be stored permanently and securely and reproducibly positioned in three positions: placement, measurement and storage.

[0037] The aforementioned control system is defined as comprising software that acquires measurements from sensors and controls electromechanical subsystems or actuators, receives user instructions from a graphical interface, as well as memory containing databases and finally wired or wireless bidirectional communication means.

[0038] According to preferred embodiments of the invention, the mobile device further comprises at least one of the following characteristics or an appropriate combination of several of them: - the device is a mobile automaton, for example a mobile trolley mounted on a plurality of casters, movable and steerable by means of one or more handles arranged at least on one front face and equipped with a braking system or motorized assistance of the casters; - said rollers are for example three in number and preferably four, one at each corner of the device, two fixed rollers at the level of a front face, user side, and two swiveling rollers at the level of a rear face, patient side, of the device; - the communication interface is a touchscreen user interface located on a top surface of the device; - the device is equipped on an essentially vertical face, patient side, with a first access via a first armored door to the first compartment intended to contain the tubing kit and a second access via a second armored door to the second compartment intended to contain the multidose vial of radiopharmaceutical product; - the unlocking and / or partial opening of the first and second armored doors can be controlled at least once a day by the operator from the communication interface; - The device includes a force sensor to detect correct filling of the kit and patient extension lines with saline via a removable hydrophobic cap located at the end of the patient extension. - The device includes components for sampling and injecting the radiopharmaceutical product: o a motorized piercing actuator to pierce the multidose vial containing the radiopharmaceutical product by moving the needle from the kit; o a motorized syringe pump to operate the syringe plunger in the kit, in order to collect a precise dose, for example with an accuracy of ±5 or ±10 pL, and then inject it into the patient diluted with physiological saline; - the device includes means for managing the opening of the doors carried out via the piercing actuator in order to ensure that the needle is properly removed from the bottle when the bottle door is opened and means to ensure that the tip of the needle is positioned in a passage that is not easily accessible to the user's fingers.

[0039] Advantageously, the activity meter includes one or more detectors of the ionization chamber type, solid detector or spectrometer type.

[0040] Advantageously, the materials used to make the kit are adapted according to the affinities of the tracers in order to avoid the retention of activity.

[0041] Advantageously, the consumables are arranged in such a way that dead volumes are minimized.

[0042] Advantageously, the kit's sampling line passes through a first bubble detector and the kit's output line passes through a second bubble detector between the vented filter and the self-sealing Luer fitting.

[0043] A second aspect of the present invention relates to a method for implementing a mobile device for the on-demand preparation of doses of radiopharmaceutical product intended for automatic intravenous administration on demand to patients, generally spread over a day as described above, characterized by the following steps: - switching on the device at the beginning of the day, if it is in standby mode; - preparing the device for the day, namely: o remove consumables including the multidose bottle, the kit, the saline container and the patient extension tube, if they are still present from the previous day, after successive openings of the second armored door and the first armored door, the bottle being removed preferably before the kit to reduce the risks of radioactive exposure; o perform the daily verification test, in particular of the activity meter using a reference source; o to install in the device, via the opening of the aforementioned doors, new consumables, namely at least respectively a multidose vial of radiopharmaceutical product, intended for several patients, as well as a tubing kit and a saline container; o to set up a patient line for each new patient; - start the automatic dose preparation procedure; - allow the tubing to fill with the saline bag and measure the activity or its concentration in the bottle, knowing precisely the volume taken; - detect the patient line; - select, correct and / or encode on the communication interface a prescribed dose for a patient; - prepare the dose, detect if it is compliant using the activity meter and proceed with the validation or return of the dose.

[0044] Advantageously, the activity meter is controlled with one or more reference sources by means of daily consistency, consistency, linearity, repeatability, reproducibility and isotope calibration tests.

[0045] Preferably, the process includes the preliminary step of connecting the device to mains power and the Ethernet network at the end of the day and then, after a certain period of inactivity, performing any necessary updates and then automatically shutting down.

[0046] Alternatively, a first aspect of the present invention relates to a mobile device for the automatic on-demand preparation and intravenous administration of a dose of radiopharmaceutical product to a plurality of patients, according to claim 1. Preferred embodiments of the device are detailed in dependent claims 2 to 9.

[0047] Alternatively, a second aspect of the present invention relates to a method for implementing a mobile device for preparing doses of radiopharmaceutical product intended for automatic intravenous administration on demand to patients, according to claims 10 and 11. Brief description of the drawings

[0048] Figures 1A to 1D represent different perspective views of the radiopharmaceutical preparation and injection apparatus according to a particular embodiment of the invention.

[0049] Figures 2A and 2B represent views of the device according to figures 1A to 1D in which the armored doors are open.

[0050] Figure 3 schematically shows the components and operation of a kit used in an automated radiopharmaceutical dose delivery device according to a particular embodiment of the invention.

[0051] Figure 4 schematically represents an example of a screenshot of the main menu of the user interface available on the touch control screen.

[0052] Figure 5 schematically represents an example of a screenshot of a user interface submenu related to device testing and calibration.

[0053] Figure 6 schematically represents an example of a screenshot of a user interface submenu specifically related to dose injection.

[0054] Figure 7 represents an example of realistic screenshots corresponding respectively to Figure 4 and Figure 6.

[0055] Figure 8A shows one embodiment of a compartment for the source of constancy for the periodic quality control required by regulations, in a "storage" position secured by a key.

[0056] Figure 8B shows the same execution form of the constancy source compartment, in a "measurement" position of the constancy source.

[0057] Figure 8C shows the same execution form of the constancy source compartment, in a "placement" position of the constancy source in the shielded housing of the compartment. Description of an embodiment according to the prior art

[0058] The prior art presents different variants of the execution of a mobile trolley equipped with an infusion / injection pump intended for the preparation and administration of a dose of radiopharmaceutical product to a patient.

[0059] Figures 1A to 1D on the one hand, and 2A and 2B on the other hand, show different views of an embodiment of an automaton 1 compatible with the prior art and serving as a basis for the presentation of the innovative features according to the invention.

[0060] As illustrated by way of example in Figures 1A to 1D, the controller 1 comprises a front face 11, a rear face 12, and side panels 13, which are essentially vertical, as well as a bottom face 14 and a top face 15, both essentially horizontal, or optionally slightly angled. The top face 15 has a control screen / user interface 16 and optionally a storage location 17, for example in the form of a trough. The aforementioned user interface 16 is preferably a touchscreen user interface. It may advantageously include an LED strip 160 (Figure 2A) on top of the screen that illuminates according to the alerts, alarms, and device statuses. The bottom face 14 has casters 18 that provide mobility for the controller, preferably four in number, one caster being located at each corner of the bottom face 14.Preferably, at least two of the wheels 18 are orientable, for example opposite the screen 16, while the other two wheels, on the side of the screen 16, are fixed.

[0061] The front part of the device is intended to be placed in front of the user (operator, nursing staff), on the side of the screen or user interface 16, and is therefore called the "user side" 21. The rear part of the device is intended to face the patient and is therefore called the "patient side" 22.

[0062] As shown in Figures 2A and 2B, handles 23 are advantageously arranged horizontally on both the front face 11 and the rear face 12, for example in pairs, to increase the equipment's maneuverability. Each of these handles 23 preferably includes a device for unlocking a handbrake to allow the equipment to be moved. This same device also allows for engaging motorized wheel assistance if the device is equipped with this option.

[0063] Preferably, the braking system consists of self-braking casters. The equipment is likely to be moved by an operator within the hospital, particularly in the positron emission tomography (PET) imaging department, from one injection room to another, where individual patients are waiting to be treated.

[0064] The front panel 11 is always equipped with a lower armored door 29 providing access to an armored vial 107 containing the radiopharmaceutical and an upper armored door 29 providing access to the internal equipment, as shown in Figure 2A (or 2B), which shows the two respective lower doors 29 and upper doors 28 open. The consumables are a multi-dose armored vial 107 (generally purchased by the customer, as is the saline bag, see below, in the dotted box in Figure 2B) containing the radiopharmaceutical to be injected into the patient, a bag of physiological saline 240, a daily kit per tracer 100, and an extension tube (or patient line) 241 for direct injection into the patient.

[0065] Accessories known in themselves are also present for the adaptation of the multidose vial such as needle centering cone 35 and shielded vial adapter 36 (Figure 2B).

[0066] Still in the example considered, a first lateral side 13, right, is equipped with a location 24 for the positioning of a physiological (saline) bag 240 generally suspended from a hook and for the connection of a patient extension line 242. The other lateral side 14, left, is equipped with a printer and an output for printed labels 27.

[0067] A tablet 26 is preferably positioned under and behind the screen 16.

[0068] For sampling and injecting the radiopharmaceutical product, the device can be equipped with the following elements known per se (see figure 2A): - a motorized piercing system 25 to pierce the vial containing the radiopharmaceutical product by moving the needle of the main consumable; - a motorized syringe pump 37 to manipulate the syringe of the main consumable, in order to collect an ultra-precise dose and then inject it into the patient in dilution with physiological saline.

[0069] Currently, the patient is often first connected to an infusion line with a saline bag to hydrate them before injection. Before starting the injection, the user connects the patient line to this infusion line, most often via a valve manifold located on the infusion line. Description of an embodiment according to the invention

[0070] The main objective of the system according to the invention is to provide a mobile automated system capable of intravenously administering, on demand, a dose of radiopharmaceutical solution for diagnostic or therapeutic purposes from a multidose vial. Specifically, the functions performed by the device and its consumables are to automatically and safely sample, measure, and administer a prescribed dose of radiopharmaceutical to the patient when the patient is connected to the patient line either via a catheter or, more commonly, to an infusion line already connected to the patient via a catheter. The device is designed for fully automated or as fully automated operation as possible.

[0071] A number of improvements to known mobile dose delivery devices have been envisaged within the scope of the invention to achieve this goal of advanced automation.

[0072] Firstly, the device has a system for measuring the activity 117 of the product in the syringe 101.

[0073] Next, consumables 107, 100, 240, and 241 are placed in a designated location on the device to ensure optimal interaction. Since the operator must be radiation-protected, equipment 1 is fitted with adequate shielding, ideally located as close as possible to the tubing, whereas in the prior art, shielding is often located on the periphery of the devices. In particular, the consumables are placed behind the two shielded doors 28 and 29. Other parts of the device may also be shielded for the same radiation protection requirements. The means of opening and / or locking these doors are known to those skilled in the art.

[0074] Advantageously, the device according to the invention uses a shielded, multi-dose tracer vial whose synthesis has been carried out beforehand outside the system (for example, in a radiopharmacy). The system uses a kit with a syringe controlled by a syringe pump that directly and accurately measures the dose drawn from the multi-dose vial and being prepared before it is injected. This is a key difference from prior art where the isotope is produced / extracted within the system itself and where the measurement is taken at the output of a generator in the injection stream.

[0075] One advantage of the multidose vial used according to the invention is that the shielding in which the vial is delivered is retained: there is no transfer to the device's shielding and therefore no breach of the shielding protection. A shielding adapter can then be advantageously used if necessary (see above).

[0076] Furthermore, according to certain unshown implementations, accessories such as a stool to assist in placing / removing the armored bottle and kit can be advantageously used to improve the ergonomics of these early morning operations (e.g., a maximum of four per day, with the remaining operations performed standing). A bottle lift could also be advantageously used to facilitate handling the heavy armored bottle (approximately 20 kg; not shown).

[0077] The diagram in Figure 3 represents, according to a particular embodiment, an example of a radiopharmaceutical kit system 100 (the kit being surrounded by a dashed line) suitable for performing tracer dosing using a syringe combined with a three-way valve. The system comprises: - a kit containing 100 items, mainly including: o a syringe 101 whose nominal capacity is for example 10mL; o a three-way valve 103; o a sampling line 106 connecting a vial of radiopharmaceutical product 107, including a needle 118 piercing the septum of the vial and tubing to the three-way valve 103. This line passes through a bubble detector 112; o a "T" 104 integrated into the three-way valve 103 and connecting a NaCl solution line 108, 240 to an outlet line 241 and to the syringe 101; o the line 108 equipped with a spike and a check valve 105, connecting the saline container 240 to the "T" 104 integrated into the three-way valve; o the outlet line 241 comprising a second check valve 105', a vented filter 111 and a self-sealing Luer fitting 113. This line passes through a second bubble detector 112'; o the ventilated filter 111 to remove any air bubbles; o a patient extender 242 of known internal volume of the control system, intended to prevent any contamination between patients. - the radiopharmaceutical product vial 107, for example with a maximum capacity of 20mL, filled with 10mL (typically for diagnostic) or 15 / 20mL (typically for therapeutic) of solution, and fitted with a septum to be pierced; the vial 107 being connected to the kit 100 once the device has moved the needle present in the kit to the bottom of the vial; - a container containing saline 240 connected to the kit via line 108 by a spike connection; - a patient extension connected downstream of the output line 241 by means of a Luer fitting 115 and comprising at its other end another Luer fitting 116, the connector 116 being suitable for connecting either to a catheter, or to a transfusion line, or to another syringe for the preparation of a dose in an external syringe 120 to the machine for the purpose of the manual administration of this dose to a patient; - an activity meter 117 located at the level of syringe 101.

[0078] The automated sequence of operations performed using kit 100 is preferably as follows: - firstly, the device fills all the lines with NaCl to remove air and facilitate dose collection; then, the device collects the entire contents of the bottle to measure the activity, knowing precisely the volume collected; this operation allows the concentration of the solution in the bottle to be deduced in order to collect precise doses based on the volume; - a given quantity of solution is taken from bottle 107 by aspiration through the sampling line 106 and via the three-way valve 103 into the syringe 101 whose piston is retracted by an actuator (not shown), the sampling line 106 being open and the injection line 241 closed by the three-way valve 103; - the concentration of the injectable solution is adjusted by withdrawing an appropriate amount of saline from the saline container 240 via the three-way valve 103, via line 108, the saline being aspirated into the syringe 101; - the possibly diluted solution is then injected via the three-way valve 103 through the outlet line 241 and possibly a patient extension 242, with the sampling line 106 closed. The vented filter 111 prevents bubbles from passing into the patient and the detector 112 verifies this; - the solution is delivered to the patient extension unit.

[0079] The device according to the invention uses a single syringe operated by a single syringe pump. By using a single syringe to perform multiple operations, the kit is simplified compared to the state of the art, which always uses several syringes.

[0080] The person skilled in the art will understand that both the design and configuration details of the apparatus and the method of administering an intravenous dose to a patient are not limited to this particular example of dosing or the use of the specific kit described above, but that other embodiments of both the apparatus or the kit and the execution of the dosing are within the scope of their general knowledge.

[0081] In summary, with a kit configured as described above, the syringe draws up an appropriate amount of stock solution, the activity in the syringe is accurately measured and corrected if necessary, and its contents are then pushed through the syringe to the outlet. Any residual activity in the syringe can still be recovered with a small amount of saline solution and pushed through the outlet.

[0082] The basic components of the injector include a precision syringe actuator and an actuator for the three-way valve (not shown), in addition to a tubing kit including two check valves as described above.

[0083] Advantageously, for the cassettes (kits) we will choose materials adapted according to the affinities of the tracers and known in themselves to the man of the trade, in order to avoid as much as possible the retention of activity in the cassettes.

[0084] The arrangement of consumables will be adapted to minimize dead volumes, for example, a dead volume of 100pL or less between the valve and syringe (at minimum dose), and 100pL or less between the syringe and the T-connector (very small flushing volumes, 4mL max). Small dead volumes reduce the total injection volume.

[0085] Given these elements, the aim is to obtain accurate samples to better than 10pL for any sample typically taken from 100pL.

[0086] Other safety, efficiency or convenience features include two bubble detectors along the tubes, a filter, a self-sealing Luer connector, a vial piercing device, a safe door opening management device, a constancy source positioning and storage device, a printer and various storage accessories.

[0087] Advantageously, the constant source will be stored permanently and securely within the device and positioned reproducibly in three locations: placement, measurement, and storage (hereinafter). In this case, advantageously, the daily constant check of the activity meter exposes the operator to virtually no radiation. Positioning the device in a shielded housing advantageously provides radiation protection from the source, and storing the source does not affect the activity meter measurements.

[0088] The automatic door opening mechanism is controlled by the piercing actuator to ensure the needle is fully ejected from the vial when the vial door is opened for insertion or removal. Furthermore, the needle is conveniently positioned in a compartment inaccessible to the user's fingers, thus preventing any risk of injury.

[0089] Figures 4 to 6 show, according to a particular form of execution, the operations that can be performed by an operator using the control screen of the device's computer system, during a typical day of use.

[0090] First, the user will turn on the device, which will be used throughout the day if necessary. Figure 4 schematically shows an example of the main menu accessible to the user, which includes several functions: dose injection procedure, dose selection, selection of a radiopharmaceutical vial, test and calibration procedures, access to an event history, and various settings (see also Figure 7). These functions correspond to different pushbuttons or touch-sensitive areas familiar to those skilled in the art.

[0091] The first step is to test the device to ensure its reliability before use (see the "Tests & Calibrations" button in Figure 4). The test mainly concerns the activity meter and in particular the consistency (activity from the same constant source compared to measurements from previous days), repeatability, reproducibility, background noise, etc.

[0092] The user must remove the consumables and the bottle so that they do not influence the test. In some cases, the consumables and bottle are left in overnight and removed early in the morning; in other cases, they are removed the night before and in the morning; the activity meter test can then be performed directly. In Figure 6, the “Bottle Characteristics” button corresponds to the “Bottle” button in Figure 7 (bottom).

[0093] If the user clicks on the "Dose Injection" function, a submenu appears, shown schematically in Figure 6. The first operation of the day is then, after opening the lower door, to remove the vial used the previous day by clicking on "Vial Characteristics" or "Vial," which unlocks and partially opens the lower door. Next, after opening the upper door, to remove the kit, patient line, and saline bag used the previous day by first clicking on "Kit Characteristics" or "Kit," which unlocks and partially opens the upper door. Optionally, the daily verification test, including the activity meter, which is mandatory, can also be performed after each kit change by clicking on "Tests" and inserting a reference source into the activity meter compartment.After the test, the operator can either remove the reference source from the activity meter, leaving it in the device (for example, in a shielded compartment), or simply remove the reference source from the equipment. Next, new consumables (saline bag, kit, and patient line) are placed using the functions described above: first, the kit, saline bag, and patient line are placed ("Kit Characteristics"), and then the bottle is placed ("Bottle Characteristics"). Once the top door is closed, the saline bag is inserted, allowing all the tubing to be filled.

[0094] A force sensor is also included to detect if the saline bag has been left in place or to monitor the proper flow of fluids within the consumables (e.g., detecting blockages / pinched tubing, detecting when saline is fully filled by monitoring the pressure increase as the saline reaches the hydrophobic filter at the end of the patient line, detecting whether the patient line is connected – if it is not, the saline reaches the self-sealing valve on the kit's injection line, etc.). This allows the saline filling to be stopped to prevent over-pressurizing the system, ensuring proper filling of the kit and patient line with saline, and preventing negligible amounts of air from entering the consumables (not shown).

[0095] A "Patient Line" indicator will show whether the patient line has been detected. Both the kit and the patient line have their own RFtag to allow automatic reading of the data on these two consumables (lot number for traceability, internal volume for proper saline filling, etc.) after the user places the tags in their slots on the device. These RFtags and bubble detectors are what detect the presence of the consumables. Conveniently, the buttons are designed to change color, indicating to the user that the consumables are correctly positioned.

[0096] Next, the operator selects a patient and the prescribed dose ("Patient," "Examination"). Before dose preparation, an optional procedure called an "Injection Test" is performed. This test injects a patient dose equivalent to the prescribed dose, but without radioactivity, using only saline at the prescribed flow rate. This is useful for patients with fragile venous systems to ensure there will be no extravasation and thus prevent the radioactive solution from leaking outside the veins (due to a poorly placed catheter, a ruptured vein, etc.). In most cases, this test is unnecessary or is already performed manually by the nurse during catheter and IV line placement.

[0097] Following this, the dose preparation process begins. Using the syringe pump allows for precise dose preparation. The dose meter displays the exact value of the prepared dose. The user can then compare the requested dose to the actual prepared dose. They also decide whether or not to inject the prepared dose by pressing the "Inject" button. If they do not wish to proceed with the injection, they can choose to "Return" the dose either to the original vial, an external shielded vial, or an external shielded syringe. Automated safeguards prevent the injection of the prepared dose if it is x% higher or y% lower than the requested dose. The device allows advanced users to bypass these safeguards through user management within the software, which includes password-protected access.

[0098] In summary, the activity meter allows the user to detect whether the dose is correct or not. If not, it "rejects" the dose ("Return"). If the dose is correct, the user connects the patient to the line and initiates the injection ("Inject").

[0099] Throughout the day, patients may come and go, and for each new patient, a new line is inserted, and the previous steps are repeated, except possibly the initial steps (replacing the bottle). When the new patient's line is inserted, the device automatically fills the saline line from the NaCl bag already in place. A saline bag lasts approximately one day or even longer. Therefore, this bag is preferably changed at the beginning of the day along with the kit and is kept throughout the day as long as the kit is not changed. It is recommended that the saline bag be changed each time the kit is changed.

[0100] Device calibration is managed via the "Test & Calibrations" submenu (Figure 5). Various tests are available for verifying the activity meter with reference sources.

[0101] Advantageously according to the invention, the long half-life reference or constancy source 220 is placed in a reproducibly and precisely location near the activity meter, in a dedicated compartment of the device 221 having a shielded housing for the source 220. Knowing the decay of this source, as well as its initial activity, the system performs a periodic measurement of this activity so as to allow the detection of any drift in the measurement made by the activity meter.

[0102] Figures 8A to 8C show, respectively, according to a preferred embodiment of the apparatus, a first position, referred to as the "storage" position, for the constant source 220, secured by a locking key 222 of compartment 221; a second position, referred to as the "measurement" position, for the constant source 220 used for reproducibility, repeatability, constancy, calibration, etc. tests; and finally, a third position, referred to as the "placement" position, for the constant source 220 in the shielded housing of compartment 221. Reference Symbols List 1 mobile injection device 11 front panel 12 rear view 13 lateral side 14 lower face 15 top face 16 User Interface 17 storage spaces 18 roulette 21 user side 22 patient side 23 handle 24 saline locations and patient line connection 25 drilling system 26 tablets 27 printer output 28 armored top door (kit) 29 lower armored door (flask) 35 needle centering cone 36 armored bottle adapter 37 syringe pump 38 rotary valve actuator 39 RFtag reader 100 radiopharmaceutical kits (with tubing) 101 syringe 102 valve-syringe connection line 103 three-way valve 104 T-tube 105, 105' non-return valve 106 line of withdrawal 107 shielded vial of concentrated radiopharmaceutical product saline connection line ventilated filter , 112' bubble detector Luer self-sealing Luer machine fitting Luer patient connector activity meter piercing needle shielding externally shielded syringe removable hydrophobic cap LED light strip source of consistency compartment of the source of constancy locking key for the compartment of the saline solution bag or bottle exit line patient extender

Claims

DEMANDS 1. A mobile device (1) for the automatic on-demand preparation and intravenous administration of a dose of radiopharmaceutical product to a plurality of patients, comprising: a first compartment to accommodate a tubing kit (100) configured to accurately prepare via several fluid paths a dose of radiopharmaceutical product diluted or not with a diluting agent such as saline (240) and to inject it directly into a patient; a second compartment to accommodate a multidose vial (107) of radiopharmaceutical product; as well as a location to accommodate a saline container (240) and the connection to a patient extension (242); the first and second compartments being at least partially shielded (119); said kit (100), the saline container (240) and said multidose vial (107) of radiopharmaceutical product being consumables configured to be replaced after treatment of one or more patients; as well as means of preparing and administering fluid using said kit (100); a control system communicating with the means of preparing and administering fluid configured to receive dose preparation information for a patient from a user and to communicate corresponding instructions to the means of preparing and administering fluid; a communication interface (16) between said controller and a user, enabling the user, via a menu of instructions, to launch a dose preparation and injection procedure, tests, calibrations, and access data in memory, for example, relating to the history of dose injections; and means of storing and printing data; said mobile device being characterized in that: said kit (100) includes a single syringe (101) configured to be controlled to dose and move fluids, a single three-way valve (103), cooperating with two check valves (105, 105'), which successively allow the radiopharmaceutical product to be withdrawn into the syringe (101), via a withdrawal line (106) comprising a first tube ending with a needle for piercing a septum of the multidose vial (107), to aspirate the radiopharmaceutical product and mix it with a quantity of saline (240) conveyed by a second tube (108) and to be injected into a patient by an outlet line (241) comprising a third tube (241), with or without the intermediary of a patient extension (242); the means for preparing and administering fluid include a precision actuator for the syringe intended to be controlled (101) and an actuator for the three-way valve (103), configured to make any direct connection between the sampling line (106) and the output line (241) impossible so that the patient is physically isolated from the multidose bottle (107); An activity meter (117) is positioned near the single syringe configured for control (101) in order to measure and validate, prior to administration, a dose prepared using said kit (100), said activity meter enabling the dose to be measured as close as possible to the patient; and The multidose vial (107) is a shielded vial containing a plurality of tracer doses prepared outside the device and inserted into the device in its original shielding.

2. The mobile device according to claim 1, characterized in that it comprises a force sensor for detecting an initial filling of the lines of the kit (100) and the patient extender (242) with saline by means of a removable hydrophobic stopper (121) located at the end of the patient extender (242).

3. The mobile device according to claim 1, characterized in that it comprises for the collection and injection of the radiopharmaceutical product: a motorized piercing actuator (25) for piercing the multidose vial (107) containing the radiopharmaceutical product by moving the needle of the kit (100); a motorized syringe pump (37) to operate the piston of the syringe in the kit (100), allowing a volume of radiopharmaceutical solution to be drawn with a volumetric accuracy of ±5% for any volume from 100pL of radiopharmaceutical solution drawn, and then injected into the patient with successive rinses of physiological saline.

4. The mobile device according to claim 1, characterized in that it comprises at least one reference or constancy source configured to control the activity meter (117), said source being able to be stored in the device permanently or not, shielded, secured against removal by any unauthorized person and reproducibly positionable in three positions: placement, measurement and internal storage outside the measurement range of the activity meter.

5. The mobile device according to claim 1, characterized in that it includes means for a door opening management (28, 29) carried out via the piercing actuator (25) to ensure that the needle is properly removed from the bottle when the door giving access to the bottle (29) is opened and means to ensure that the tip of the needle is positioned in a passage that is difficult or impossible for the user's fingers to access.

6. The mobile device according to claim 1, characterized in that the activity meter (117), measuring the activity of the syringe, comprises one or more detectors of the ionization chamber type, solid detector or spectrometer.

7. The mobile device according to claim 1, characterized in that the materials used to make the kit are adapted according to the affinities of the tracers in order to avoid the retention of activity.

8. The mobile device according to claim 1, characterized in that the consumables are arranged in such a way that the internal dead volumes of the kit are minimized.

9. The mobile device according to claim 1, characterized in that the kit sampling line (106) passes through a first bubble detector (112) and the kit outlet line (241) passes through a second bubble detector (112') between the vented filter (111) and the self-sealing Luer fitting (113).

10. A method for implementing a mobile device for the on-demand preparation of doses of radiopharmaceutical product intended for automated intravenous administration to patients, generally spread over a day, according to any one of the preceding claims, characterized by the following steps: - turn the device (1) on at the start of the day, if it is in standby mode; - prepare the device (1) for the day, namely: o remove the consumables including the multidose bottle (107), the kit (100), the saline container (240) and the patient extension (242) previously used, after successive openings of the second armored door (29) and the first armored door (28), the bottle (107) being preferably removed before the kit (100) to reduce the risks of radioactive exposure; o perform the daily verification test, in particular of the activity meter (117) using a reference source; to place in the device, via the opening of the aforementioned doors (28, 29), new consumables, namely at least respectively a multidose vial (107) of radiopharmaceutical product, intended for several patients, as well as a tubing kit (100) and a saline container (240); o to set up a patient extender (242) for each new patient; - Start the automatic dose preparation procedure: o the tubes fill with saline; o the activity or its concentration in the bottle are measured thanks to the precise knowledge of the volume taken; o the outlet line (241) and the possible patient extension (242) are detected and filled; - select, correct and / or encode on the communication interface (16) a prescribed dose for a specific patient; - the device prepares the dose, detects if it is compliant by means of the activity meter (117) and proceeds to validate or return the dose.

11. The method of implementing the apparatus according to the preceding claim, characterized in that the activity meter (117) is controlled with one or more reference sources by means of daily consistency, consistency, linearity, repeatability, reproducibility and isotope calibration tests.

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