Seeds and applicators for radiation therapy

Abstract

A casing holding one or more brachytherapy seeds for implantation into a patient, the seeds carrying atoms of a radioactive element for radiation therapy, the casing being filled with a viscous liquid to prevent radiation from the one or more brachytherapy seeds from exiting the casing. The casing can include a metallic or non-metallic elongated tube configured for insertion into body tissue, or a vial for insertion into a needle for delivery of the seeds to a physician. [Selected Figure] Figure 2

Description

Technical Field

[0001] The present invention generally relates to radiation therapy, and more particularly to a method of applying alpha particle seeds to a patient.

Background Art

[0002] Brachytherapy is a powerful means for the radiation therapy of tumors, including malignant tumors. The proper delivery of seeds with embedded particle emitters is important for the success of treatment. Delivery requires accurate placement of the seeds within the tumor without premature exposure of the patient and other tissues to radioactive and other unhealthy substances.

[0003] U.S. Patent Application Publication 2015 / 0375011 (Patent Document 1), the entire disclosure of which is incorporated herein by reference, describes a brachytherapy seed with a bimetal strip that "curls" when exposed to body temperature to fix the seed in place.

[0004] In many cases, brachytherapy devices are permanently implanted in the tumor and not removed.

[0005] U.S. Patent Application Publication 2003 / 0088144 (Patent Document 2), Terwilliger et al., Title: "Improved Delivery System and Method for Interstitial Radiation Therapy Using Hollow Seeds", the disclosure of which is incorporated herein by reference in its entirety, suggests the use of a bioabsorbable seed strand onto which a plurality of tubular hollow radioactive seeds are attached.

[0006] In other cases, brachytherapy devices are what is called temporary brachytherapy and are usually implanted for a short period of up to several hours.

[0007] U.S. Patent No. 9,272,160 (Patent Document 3) to Kader et al., the entire disclosure of which is incorporated herein by reference, describes a brachytherapy strand with a tether that can be used for strand removal.

[0008] U.S. Patent Application Publication 2010 / 0249487 (Patent Document 4), the disclosure of which is incorporated herein by reference in its entirety, describes a flexible brachytherapy device implanted in the body with a tail extending outside the body. The tail can be used to remove the brachytherapy device at the end of treatment.

[0009] It has been proposed to use a hollow needle and a stylet to deliver seeds to the implant position of a tumor.

[0010] Ferguson's U.S. Patent Application Publication 2003 / 0191355 (Patent Document 5), the entire disclosure of which is incorporated herein by reference, describes the delivery of a seed array to a needle using a stylet.

[0011] Lamoureux's U.S. Patent Application Publication 2008 / 0269540 (Patent Document 6), the disclosure of which is incorporated herein by reference in its entirety, promotes a seed and any spacers from a seed cartridge assembly through a hollow needle to the distal end of the hollow needle and retracts the hollow needle while the stylet is held in place, thereby placing the seed and any spacers in the desired position. Long stylets and short stylets are referenced.

[0012] Hoskins et al.'s U.S. Patent No. 6,752,753 (Patent Document 7), the disclosure of which is incorporated herein by reference, describes a needle and a stylet for delivering seeds to a tumor.

[0013] An important issue in the use of brachytherapy devices is the protection of healthy tissue from unwanted radiation.

[0014] U.S. Patent Application Publication 2014 / 0048729 (Patent Document 8), the disclosure of which is incorporated herein by reference in its entirety, describes a lightweight protection device worn on sensitive body organs.

[0015] U.S. Patent Application Publication 2018 / 0082760 (Patent Document 9), the disclosure of which is incorporated herein by reference in its entirety, describes a transparent radiation shield.

Prior Art Documents

Patent Documents

[0016]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Patent Document 5

Patent Document 6

Patent Document 7

Patent Document 8

Patent Document 9

Summary of the Invention

[0017] One aspect of some embodiments of the present invention is an apparatus for brachytherapy, comprising a casing; one or more brachytherapy seeds for implantation in a patient, carried within the casing and carrying atoms of a radioactive element for radiotherapy treatment; and a viscous liquid within the casing that prevents radiation from the one or more brachytherapy seeds from exiting the casing. Optionally, the casing has a needle. Alternatively, the casing further comprises a seed applicator having a tube adapted for insertion into a patient and a stylet within the tube. Or, the casing has a seed capsule having a needle port at a first end and a piston carrying one or more brachytherapy seeds at a second end, and movement of the piston extrudes the one or more brachytherapy seeds into the needle within the needle port.

[0018] Optionally, the viscous liquid has glycerin. Optionally, the casing has a hub at the proximal end of an elongate tube, the hub having an empty chamber configured to collect excess viscous liquid from the elongate tube when the viscous liquid expands due to heat sterilization. Optionally, the distal end of the hub connecting to the elongate tube has a funnel shape configured to allow viscous liquid from the elongate tube entering the hub to return to the elongate tube. Optionally, the needle port is configured to receive the needle in an orientation such that one or more brachytherapy seeds enter the needle along with a portion of the viscous liquid.

[0019] According to an embodiment of the present invention, there is further provided a method of attaching a brachytherapy seed to a needle, comprising the steps of gripping a needle having a sharp tip for entering tissue in a manner that prevents movement of the needle; bringing the brachytherapy seed to a point adjacent to the tip of the needle; and pushing the brachytherapy seed into the needle via the sharp tip.

[0020] Optionally, the step of pushing the brachytherapy seed into the needle comprises pushing a stylet that pushes the seed into the needle.

[0021] According to an embodiment of the present invention, there is further provided a seed loading device for brachytherapy, comprising: a central chamber for storing brachytherapy seeds; a needle port configured to fix a needle in a direction such that a sharp tip of the needle is aligned with the brachytherapy seeds in the central chamber; and a piston configured to push the brachytherapy seeds into the needle fixed to the needle port.

[0022] As an option, the central chamber further stores a viscous liquid to prevent radon released by the brachytherapy seeds from leaving the loading device. As an option, the needle port has a screw for fixing the needle to the needle port when tightened. As an option, it further has a piston screw that pushes the piston towards the central chamber when rotated.

[0023] According to an embodiment of the present invention, there is further provided a brachytherapy seed applicator, comprising: a non-metallic elongated tube configured for insertion into tissue; a hub at the proximal end of the tube; one or more brachytherapy seeds carrying radioactive particles within the tube; and a stylet inserted into the tube and configured to push the one or more brachytherapy seeds towards the distal end of the elongated tube.

[0024] As an option, the one or more brachytherapy seeds carry alpha-emitting particles. As an option, the one or more brachytherapy seeds carry radium seeds. As an option, the non-metallic elongated tube enables observation of the one or more brachytherapy seeds within the ultrasonic image of the applicator. As an option, the non-metallic elongated tube prevents daughter nuclei of the radioactive particles from exiting the non-metallic elongated tube. As an option, the one or more brachytherapy seeds are at least 1 centimeter away from the distal tip of the non-metallic elongated tube. As an option, the non-metallic elongated tube contains Kapton.

[0025] According to an embodiment of the present invention, there is provided a stopper for controlling the movement of a stylet relative to a brachytherapy needle, comprising: a body structure; a first connector on the body structure for gripping the needle hub of the brachytherapy needle; a second connector on the body structure for gripping the stylet hub to prevent the stylet from moving distally; and a third connector on the body structure for gripping the stylet hub to prevent the stylet from moving both proximally and distally.

[0026] Optionally, the first connector comprises a slot configured to grip the needle hub. Optionally, the second connector is configured to prevent distal movement of the stylet without impeding proximal movement of the stylet. Optionally, the second and third connectors are configured to grip the stylet hub at different axial positions relative to the needle. Optionally, the body structure is expandable to change the axial positions at which the second and third connectors grip the stylet hub.

[0027] According to an embodiment of the present invention, there is provided a method for inserting a brachytherapy seed into body tissue, comprising: providing a needle having a brachytherapy seed therein, wherein the stylet is inserted through the proximal end of the needle and the stopper holds the hub of the stylet in the first connector of the stylet, thereby preventing movement of the stylet both distally and proximally relative to the needle; inserting the tip of the needle into the tumor; pushing the hub of the stylet from the first connector to the second connector, thereby preventing the hub of the stylet from moving distally to an axial position of the hub of the stylet different from the first connector; and removing the stopper and retracting the needle proximally relative to the stylet to leave the seed in the tumor.

[0028] According to an embodiment of the present invention, there is further provided a brachytherapy implant comprising: a hollow biocompatible wire; at least one tubular seed attached to the hollow biocompatible wire and defining an internal channel; and radioactive particles for radiotherapy disposed in the at least one tubular seed.

[0029] Optionally, the hollow biocompatible wire defines an internal channel having a diameter of less than 0.5 millimeters. Optionally, the hollow biocompatible wire is not biodegradable. Optionally, at least one tubular seed is disposed in the center of the hollow biocompatible wire, at least 10 millimeters away from both ends of the hollow biocompatible wire.

[0030] According to an embodiment of the present invention, there is further provided a method of inserting a brachytherapy seed into body tissue, comprising: inserting a needle through a first point into the body tissue until the tip of the needle exits the tissue at a second point; extruding the distal end of a strand carrying one or more brachytherapy seeds from the distal tip of the needle; gripping the distal end of the strand; and withdrawing the needle proximally from the tissue while gripping the distal end of the strand so that one or more brachytherapy seeds remain in the tissue. Optionally, the method further comprises pulling the distal end of the strand to adjust the position of one or more brachytherapy seeds within the tissue. Optionally, the step of gripping the distal end of the strand comprises gripping with forceps. Optionally, the step of inserting the needle into the body tissue comprises inserting a needle having the strand inside. BRIEF DESCRIPTION OF THE DRAWINGS

[0031]

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DETAILED DESCRIPTION OF THE INVENTION

[0032] One aspect of some embodiments of the present invention relates to the packaging of radiotherapy seeds within a package, where they are surrounded by a viscous liquid that prevents unwanted dissipation of particles from the seeds. Optionally, the viscous liquid prevents the release of daughter nuclei such as radon (Rn)-220. As an option, the viscous liquid does not boil during heat sterilization. In some embodiments, the viscous liquid includes biocompatible glycerin, optionally USP Class VI glycerin.

[0033] In some embodiments, the seeds are provided pre-loaded into the elongated delivery tube of the applicator device, and the elongated delivery tube is filled with a viscous liquid. The viscous liquid collects the daughter nuclei released from the seeds. When the seed is inserted into the tumor, the viscous liquid enters the tumor with the seed, and the radioactive daughter nuclei in the viscous liquid participate in the treatment of brachytherapy.

[0034] In some embodiments, the elongated tube is a flexible tube that can be used to reach locations that are difficult to reach with a rigid needle. In other embodiments, the elongated delivery tube includes a needle that defines an internal delivery channel. Alternatively, the seeds are pre-loaded onto a delivery wire within the tube, such as a biocompatible suture thread or a metal (e.g., stainless steel, nitinol) wire.

[0035] The applicator device optionally includes a biocompatible hub proximal to the needle or other elongated tube for collecting the viscous liquid during heat sterilization. The distal end of the biocompatible hub that connects to the needle or other elongated tube optionally has an internal surface in the shape of a funnel, and after heat sterilization is complete, the viscous liquid can be simply returned to the elongated tube. To minimize the amount of viscous liquid that leaves the elongated tube during sterilization, it is preferable to hold the applicator with the distal end of the elongated tube facing downwards.

[0036] In other embodiments, the seeds are provided in a sealed capsule filled with glycerin and designed to allow easy loading of the seeds onto the needle. The capsule has a needle adapter head defined to receive the needle in an orientation that loads the seed onto the needle along with a portion of the glycerin. Thus, the brachytherapy seeds are protected by the viscous liquid through delivery and loading onto the needle or other applicator.

[0037] One aspect of some embodiments of the present invention relates to loading a brachytherapy seed into a needle applicator from the distal end of the needle (i.e., the end to be inserted into the patient), rather than from the proximal end. Loading the needle from the distal end shortens the distance the seed has to travel through the internal channel of the applicator, reducing the potential for damage by such a passage.

[0038] One aspect of some embodiments of the present invention relates to a capsule for loading a brachytherapy seed into an applicator. The capsule is configured to hold a brachytherapy seed within a sealed chamber. Optionally, a first end of the chamber is adapted to receive a needle, and the other end includes a piston configured to push the seed into the needle received through the first end.

[0039] One aspect of some embodiments relates to an applicator device including a non-metallic tube configured to deliver one or more alpha-emitting brachytherapy seeds to human tissue. The non-metallic tube is configured to prevent the emission of alpha from the tube, thus preventing premature emission of radiation to healthy tissue. Using a non-metallic tube allows the seed to be accurately positioned using an imaging modality such as ultrasound, while the seed is inside the tube and cannot emit alpha to healthy tissue. Optionally, the seed is at least 3 millimeters, at least 5 millimeters, or even at least 9 millimeters away from the distal end of the tube to prevent radiation leakage from the distal end of the tube.

[0040] Optionally, after the position of the seed within the tumor has been confirmed, for example by ultrasound or computed tomography (CT), the applicator tube is removed from the patient's tissue. Removal of the tube activates the brachytherapy treatment, allowing the alpha nuclei and daughter nuclei from the seed to reach the patient's tissue. The transparent elongated tube optionally includes a polymer such as Kapton. Alternatively, the tube is formed of another suitable biocompatible polymer that is durable at the heat and / or radiation levels used for sterilization, such as biocompatible polyetheretherketone (PEEK).

[0041] In some embodiments, the applicator device includes a mechanism for controlling the position of a seed within an elongate tube relative to the distal end of the tube. As an option, in an initial state, the seed is held within the elongate tube at a distance from the distal end of the elongate tube. The sealing cap prevents radon or other materials from exiting the distal end of the tube. After the position of the distal end of the tube relative to the tumor has been confirmed, the applicator device is used to move the seed to the distal end of the elongate tube. Thereafter, the elongate tube is retracted in the proximal direction, leaving the seed in position within the patient's body.

[0042] One aspect of some embodiments relates to a stopper for controlling the movement of a stylet relative to the elongate tube of an applicator, which has at least one state that limits or prevents both proximal and distal movement. As an option, the stopper further has at least one state in which the stopper limits only distal movement and does not limit proximal movement.

[0043] One aspect of some embodiments of the present invention relates to a brachytherapy implant that includes one or more tubular seeds carrying a particle emitter, mounted on a delivery wire. In some embodiments of the present invention, the delivery wire consists of a hollow tube. Using a hollow tube as the delivery wire allows the wire to be easily fixed by pressing the wire in such a way that the non-pressed portion of the wire bulges outward.

[0044] One aspect of some embodiments relates to a method of implanting a brachytherapy seed in a patient. The method includes inserting a delivery strand carrying the seed into an organ of the body with a needle that enters the organ from one side and exits from another side. The physician grasps the distal end of the delivery strand and adjusts the position of the seed by moving the distal end of the delivery strand.

[0045] In some embodiments, the needle is inserted into the organ with the delivery strand encapsulated within the needle. Alternatively, the strand is inserted into the needle after the needle has been inserted into the organ. For example, the delivery strand may pass through a flexible tube and be threaded through a separate needle that has been pre-inserted into a body organ.

[0046] Figure 1 is a schematic view of a Diffusion Alpha-Emitter Radiotherapy (DaRT) implant 100 according to an embodiment of the present invention. The implant 100 includes a delivery wire 104 with one or more brachytherapy seeds 102 attached thereto. Each seed 102 consists of a cylindrical tube with an internal tunnel through which the delivery wire 104 passes. In Figure 1, a delivery wire 104 having two seeds 102 is shown, but the delivery wire 104 may have any suitable number of seeds depending on the specific patient needs, including a single seed 102 or multiple seeds 102, in some cases three or more or five or more. The delivery wire 104 is optionally flexible and can be bent as needed to conform to the patient in the regions along its length not covered by the seeds 102. By attaching the seeds on the wire 104, it becomes possible to insert multiple seeds 102 into the patient together. The delivery wire 104 can be used to fix the seeds 102 in place within the patient and / or to remove the seeds 102 from the patient after a treatment session.

[0047] Each seed 102 has a length of, as an option, at least 0.2 centimeters, 0.5 centimeters, or even at least 0.8 centimeters. Optionally, the seed 102 is shorter than 2.1 centimeters, or shorter than 1.5 or 1.2 centimeters. In some embodiments, the seed 102 has a length of about 1 centimeter. The seed has, as an option, an outer diameter of at least 0.3 millimeters, at least 0.5 millimeters, or even at least 0.6 millimeters. In some embodiments, the seed 102 has an outer diameter of about 0.7 millimeters, while in other embodiments, the seed 102 has an outer diameter of 0.35 millimeters. The inner diameter of the seed 102 is, as an option, greater than 0.2 millimeters, greater than 0.4 millimeters, or even greater than 0.5 millimeters. In some embodiments, the inner diameter of the seed 102 is less than 2 millimeters, less than 1 millimeter, or even less than 0.5 millimeters. In some embodiments, the inner diameter is about 0.25 millimeters or 0.4 millimeters. The tubular seeds 102 have, as an option, a length of at least 2 times, at least 5 times, or even at least 10 times their outer diameter. The seed 102 is made of, as an option, stainless steel, such as 316LVM stainless steel, titanium, nitinol, and / or any other suitable biocompatible conductive material.

[0048] The delivery wire 104 has an outer diameter that is approximately the same size as the inner diameter of the seed 102. In some embodiments, the outer diameter of the wire 104 is smaller than the inner diameter of the seed 102, so the wire 104 moves freely within the seed. In other embodiments, the diameter of the wire 104 is substantially equal to the inner diameter of the seed 102, so the seed 102 does not move relative to the wire 104 without applying at least a predetermined force. The difference between the inner diameter of the seed 102 and the outer diameter of the wire 104 is, as an option, greater than 5 microns, greater than 15 microns, or even greater than 25 microns. The difference between the inner diameter of the seed 102 and the outer diameter of the delivery wire 104 is preferably less than 60 microns, less than 40 microns, or even less than 30 microns.

[0049] The delivery wire 104 is made of a metal such as nitinol or stainless steel, such as 316LVM stainless steel, as an option. As an option, the wire 104 is made of a biocompatible suture. For example, the delivery wire 104 may be made of a polymer thread such as polypropylene, polyester, polytetrafluoroethylene (PTFE) and / or PEEK. The delivery wire 104 is, as an option, formed of a biodegradable material. As an option, the delivery wire 104 is not biodegradable and the seed 102 can be removed from the patient using the delivery wire 104 after the treatment interval. The treatment interval can be, as an option, at least one week, at least one month, or even at least three months.

[0050] As an option, the seeds 102 are fixed to the delivery wire 104 to prevent their sliding thereon using any suitable method known in the art. In some embodiments, the delivery wire 104 includes a biocompatible polymer thread that expands to prevent the seed 102 from sliding along the delivery wire 104. As an option, or in addition, the seed 102 is fixed on the delivery wire 104 by distortion of the delivery wire 104, such as a knot at the end of the seed 102.

[0051] In some embodiments, the delivery wire 104 is formed of a material that expands when heated. After the delivery wire 104 is inserted into one or more seeds 102, the wire is heated, thereby fixing the wire to the seeds. In some embodiments, the delivery wire 104 consists of a hollow tube that can be easily deformed by the physician so that it can be used for fixing the delivery wire 104 as described below.

[0052] The seeds 102 on the delivery wire 104 may be separated from each other or adjacent to each other, and the distance between the ends of adjacent seeds 102 can be very small (for example, less than 0.5 millimeter or even less than 0.05 millimeter).

[0053] In some embodiments, one or more seeds 102 are attached in the middle of the delivery wire 104 such that free ends of the delivery wire 104 are left on both sides of the seed 102. Optionally, the ends of the delivery wire not covered by the seed 102 have a length of at least 5 millimeters, at least 10 millimeters, and even at least 20 millimeters. Thus, a physician can use both ends of the delivery wire 104 to adjust the position of the seed 102 within the tumor and / or fix the seed 102 within the tumor. Further, after the treatment period, the delivery wire 104 can be used to remove the seed 102 from the patient.

[0054] In other embodiments, one or more seeds 102 are attached to the ends of the delivery wire 104, which functions as a tail for adjustment and / or fixation of the seed position and / or removal of the seed after the procedure is completed.

[0055] The seed 102 is loaded with radioactive material particles. Optionally, the radioactive material contains alpha-emitting atoms on the outer surface of the seed 102. The particles are loaded onto the seed using any method known in the art, including the methods described in U.S. Patent No. 8,834,837 to Kelson et al. entitled "Methods and Apparatus for Radiation Therapy" and U.S. Patent Application Publication 2009 / 0136422 to Kelson et al. entitled "Radioactive Surface Sources and Methods for Producing the Same". In some embodiments, the seed carries radium-223 or radium-224 particles. Optionally, the seed carries other suitable particles such as radon-219, radon-220, or thorium-228. Optionally, the seed 102 can contain up to 5 μCi and / or up to 185 kBq of radium 224. However, in other embodiments, the seed 102 is loaded with other amounts of radioactive material or other radioactive materials that emit other particles such as beta or gamma particles.

[0056] Figure 2 is a schematic view of an applicator 200 for delivering one or more seeds 102 to a patient's location, according to an embodiment of the present invention. The applicator 200 includes an elongated hollow tube 202 configured to receive the implant 100 and having a proximal tube hub 204 that functions as a handle. The applicator 200 further includes a stylet 210 configured to be inserted into the elongated hollow tube 202. The stylet 210 has a proximal stylet hub 212 that at least partially fits within a hollow channel in the tube hub 204. Optionally, a safety screw 220 is used to fix a hole 206 in the tube hub 204 to a corresponding hole 216 in the stylet hub 212, thereby fixing the distal end of the stylet 210 at a predetermined position within the tube hub 204 or within the proximal portion of the elongated hollow tube 202. Optionally, a protective cap 222 covers the elongated tube 202 during handling.

[0057] In some embodiments, the elongated hollow tube 202 consists of a rigid needle, such as a stainless steel needle. Alternatively, the elongated hollow tube 202 consists of a flexible tube, such as a Kapton tube, for example a transparent Kapton tube, allowing the physician to view the seeds 102 within the elongated hollow tube 202. Optionally, in this alternative, a separate hollow needle of any desired shape (e.g., straight, curved) is inserted into the patient to insert the tube 202 into the patient.

[0058] The delivery wire 104 is, optionally, fully retained within the elongate tube 202. The elongate tube 202 is brought to the desired implant location for inserting one or more seeds 102 on the delivery wire 104 into a patient. Next, the safety screw 220 is removed and the stylet 210 is pushed forward to extrude the distal portion of the delivery wire 104 from the distal end of the elongate tube 202. The use of the stylet 210 to extrude the delivery wire 104 from the elongate hollow tube 202 allows the seed 102 to move away from the distal end of the elongate tube 202 during transport and prior to actual use, thereby preventing unwanted radiation leakage. Optionally, during transport, the distal end of the most distal seed 102 of the elongate hollow tube 202 is at least 1 centimeter or even 1.5 centimeters away from the distal end of the elongate hollow tube 202.

[0059] The stylet 210 is, in some embodiments, shorter than the needle 202 such that the distal tip of the stylet 210 does not reach the distal end of the needle 202. Optionally, a certain stylet 210 has a length suitable for pushing the delivery wire 104 distally to the point where a small portion of the distal end of the delivery wire 104 protrudes from the needle 202. The stylet 210, optionally, has a length sufficient to push the proximal end of the delivery wire 104 to the point where the distal end of the delivery wire 104 slightly protrudes from the needle 202. The extent to which the delivery wire 104 protrudes from the needle 202 after being pushed by the stylet 210 is, optionally, less than 20 millimeters, less than 10 millimeters, or even less than 8 millimeters. Optionally, the length of the stylet 210 is slightly longer than the difference between the length of the needle 202 and the shortest delivery wire 104 that is considered to be disposed within the needle 104. Alternatively, the stylet 210 has a length suitable for pushing the seed 102 distally, for example, equal to the difference in length between the needle 202 and the seed 102. The use of a short stylet is particularly feasible when the needle is inserted into a body organ and exits from the opposite side of the body organ. In such a case, the physician can easily access the distal end of the delivery wire 104 protruding from the needle 202 and thus can adjust the position of the seed 102 without using the stylet 210.

[0060] In some embodiments, the applicator 200 includes an inlet seal 236 at the proximal end of the elongate tube 202 or at the distal portion of the tube hub 204 near the proximal end of the elongate tube 202. The inlet seal 236 prevents radon gas generated within the elongate tube 202 from exiting proximally from the elongate tube 202. Alternatively, the inlet seal 236 consists of a Wilson seal that maintains its sealing properties even when the stylet 210 passes through the inlet seal 236 and into the elongate tube 202. Alternatively, the inlet seal 236 includes an extended foil. Further alternatively, the inlet seal 236 consists of any other suitable seal, such as any conforming seal described in "Investigation of Actuator Shaft Sealing Technology for Extended Space Missions" by G.M Hofz, National Aeronautics and Space Administration, December 15, 1972, the disclosure of which is incorporated herein by reference. The applicator 200 optionally also has a distal seal 238 at the distal end of the elongate tube 202. The distal seal 238 includes, for example, a beeswax plug or a biocompatible foil and prevents the outflow of radon gas from the distal end. Alternatively, any other suitable sealing material that can be easily removed when the implant 100 exits the elongate tube 202 can be used.

[0061] FIG. 3 is a flowchart of the acts performed when delivering a DaRT implant to a tumor in a patient's arm 402 (FIG. 4) according to an embodiment of the present invention. The implantation process begins with the step of removing the protective cap 222 from the elongate hollow tube 202 (FIG. 2) of the applicator (step 302). The elongate hollow tube 202 is inserted into the patient's arm where the tumor is located (step 304). In embodiments where the elongate hollow tube 202 is a needle, the needle is inserted directly into the arm. In other embodiments, a separate needle is inserted into the patient's arm and the elongate hollow tube 202 is inserted into the separate needle.

[0062] When it is determined that the distal end of the elongated hollow tube 202 is properly positioned (step 306), for example, by removing the safety screw 220, the fixation of the stylet 210 to the elongated hollow tube 202 is removed (step 308). Thereafter, while holding the tube hub 204, the distal end of the stylet 210 is pushed distally against the implant 100, whereby the distal end of the delivery wire 104 exits the elongated tube 202 as the stylet hub 212 is pushed distally (step 310).

[0063] Figure 4A is a schematic view of the applicator 200 during delivery of the DaRT implant to a tumor in a patient's arm 402, according to an embodiment of the present invention. Figure 4A shows the applicator 200 after the stylet hub 212 has been pushed distally (step 310).

[0064] The physician grasps the distal portion of the delivery wire 104, for example using forceps (step 312), the applicator 200 is removed proximally from the patient, and the delivery wire 104 and one or more seeds 102 remain within the patient's arm 402. The wire 104 is moved and its position adjusted as necessary (step 314), and once properly positioned, the delivery wire 104 is secured in place (step 316).

[0065] In some embodiments, the fixation of the delivery wire (step 316) is achieved using fixation buttons on both sides. Any suitable fixation button, such as the button described in U.S. Patent No. 2,075,508 entitled "Suture Retainer" by Davidson, the disclosure of which is incorporated herein by reference in its entirety, may be used. Alternatively, after placing a fixation button at the end of the wire 104, the wire adjacent to the button is deformed to hold the button against the patient. As described above, in some embodiments, the wire 104 consists of a hollow tube. In these embodiments, alternatively, the wire 104 is deformed by pressing the wire using forceps or any other suitable tool, expanding the side of the wire where no pressure is applied outwardly.

[0066] Figure 4B is a schematic diagram of fixing the implant 100 (FIG. 1) to the patient's arm 402 according to an embodiment of the present invention. FIG. 4B shows a first button 406A already disposed at the proximal end of the delivery wire 104 and a second button 406B ready for installation. To fix the button, forceps 404 are used to press a clip that fixes the button in place. Alternatively, as described below with reference to FIG. 10, a button that functions as a clip is used and forceps 404 are used to press the button. Further alternatively, the delivery wire 104 itself is deformed so as to fix the button in place. In an embodiment where the delivery wire 104 is hollow, the pressure on the delivery wire causes the wire to indent at the point where the pressure is applied and deform the wire so as to expand where no pressure is applied. Thereby, the first button 406A is prevented from falling off the delivery wire 104. In other embodiments, the fixation is achieved by bending the delivery wire 104 laterally. As an option, in an embodiment where the delivery wire 104 consists of a flexible suture, the fixation is achieved by tying the suture.

[0067] Instead of, or in addition to, using an inlet seal 236 and / or a distal seal 238 to prevent the emission of radiation from the seed 102 during processing, the hollow tube 202 is filled with a viscous liquid that prevents the emission of radon particles. Further, if it is determined that the seed is not properly positioned, the viscous liquid creates a vacuum effect that sucks the seed 102 that has partially exited the hollow tube 202 back into the hollow tube 202. This vacuum effect is particularly useful in embodiments where the hollow tube 202 is metallic and no other means described herein are used for the precise positioning of the seed 102. Alternatively, after determining (step 306) that the tip of the needle and the seed 102 are properly positioned using available means, the physician presses the stylet 210 by an amount necessary to partially exit the seed from the distal tip of the hollow tube 202. Next, the position of the seed 102 is confirmed and a determination is made as to whether to continue to extrude the seed from the elongate tube 202 or to suck the seed 102 back into the elongate tube 202 and adjust the position of the tip of the tube 202 to more precisely release the seed 102.

[0068] Alternatively, the viscous liquid comprises a biocompatible material that can withstand sterilization at about 160 degrees Celsius. In some embodiments, the viscous liquid has a viscosity of at least 10, 20, or even 50 centipoise (cP) at 20 degrees Celsius. Optionally, the viscous liquid comprises glycerin, such as USP Class VI glycerin. Glycerin, optionally, has a water content of less than 5%, less than 2%, or even less than 1%. In some embodiments, the proximal tube hub 204 defines an internal air chamber designed to collect excess viscous liquid from the elongate hollow tube 202 when the viscous liquid expands due to heat sterilization. Alternatively, the distal end of the proximal tube hub 204 that connects to the elongate tube 202 has a funnel shape 226 configured such that viscous liquid from the elongate tube entering the hub 204 can return to the elongate tube 202.

[0069] Optionally, glycerin is loaded into the elongate hollow tube 202 from the distal end of the elongate hollow tube 202. As an alternative, a syringe holding glycerin is connected to the distal end of the elongate hollow tube 202 and the glycerin is pushed from the syringe into the tube 202.

[0070] The viscous liquid may completely fill the elongate hollow tube 202 or may only fill a portion of the tube 202 surrounding the seed 102. As an alternative, the viscous liquid covers at least 10 millimeters from both sides of the seed 102.

[0071] FIG. 5 is a schematic view of an applicator 500 according to another embodiment of the present invention. Similar to the applicator 200, the applicator 500 includes a needle 502, a needle hub 504, a stylet hub 506 and a stylet (not shown) at the distal end of the stylet hub 506 within the needle hub 504. The stylet is intended to be longer and have approximately the length of the needle 502, allowing the physician to push the entire contents of the needle 502 out of the needle. Thus, the applicator 500 can be used to insert one or more seeds into a patient at a location where the needle 502 does not exit the patient from the opposite side and the seed 102 and / or the delivery wire 104 cannot be pulled from the opposite side. In some embodiments, the applicator 500 includes a depth adapter 510 used to adjust the length of the needle 502 inserted into the patient. Optionally, the depth is adjusted by rotating the depth adapter 510 around the threads on the outer surface of the needle hub 504.

[0072] In some embodiments, the applicator 500 is used in conjunction with a template that defines the location where the seed is inserted. This is described, for example, in U.S. Patent Application Publication 2017 / 0319871 entitled "Brachytherapy fiducial needle fixation system" by Pitman, and / or U.S. Patent Application Publication 2014 / 0296612 entitled "Brachytherapy assistance device" by Schwarz, the disclosures of which are incorporated herein by reference in their entirety.

[0073] In some embodiments, the applicator 200 and / or 500 are provided to the physician with one or more seeds 102 pre-loaded. In these embodiments, the physician only needs to insert the needle of the applicator into the patient. In other embodiments, the physician loads one or more seeds 102 onto the needle. Optionally, the needles of the applicator 200 and / or 500 are supplied without pre-loaded seeds 102, and the physician loads the desired number of seeds 102 onto the needle. Alternatively, the needle is supplied with a minimum number of seeds, such as one seed, pre-loaded, and the physician loads one or more additional seeds as needed.

[0074] Needle FIG. 6 is a schematic view of a seed vial 600 according to an embodiment of the present invention. The seed vial 600 includes a tube 602 that defines a narrow central chamber 604 on one side designed to hold the brachytherapy seed 102, and a wide chamber 606 configured to receive a piston 608 on the opposite side, which pushes the seed 102 held within the narrow chamber 604 into the needle. An O-ring 620 is optionally disposed towards the end of the piston 608, such that when the piston 608 is pushed into the wide chamber 606, the liquid within the wide chamber 606 is pushed into the narrow chamber 604. The outer surface of the tube 602 on the side of the wide chamber defines a thread 610, which mates with a piston screw 612 that can be screwed onto the thread 610 in a manner that pushes the piston 608 into the wide chamber 606. The seed vial 600 further includes a needle adapter 614 and a needle screw 616. The needle adapter 614 includes a receptacle 622 having internal threads on one side that are screwed onto corresponding threads 624 on the tube 602. At the opposite end, the needle adapter 614 includes an elastic member 628 having external threads 618. When the internal threads of the needle screw 616 are screwed onto the external threads 618 of the needle adapter 614, the elastic member 628 is pushed inwards, narrowing the internal needle channel 630 of the needle adapter 614. When the needle is within the needle channel 630, the pressure on the elastic member 628 prevents the needle from moving.

[0075] Optionally, the tube 602 is filled with glycerin to prevent radiation from the seed 102 from leaking out of the seed vial 600. The seed vial 600 includes a piston screw 612 screwed only into the limited end of the thread 610 and a needle screw 616 screwed only into the limited end of the thread 618. To load the seed 102 in the seed vial 600 onto the needle, the needle is inserted into the narrow chamber 604 of the tube 602 via the needle screw 616 and the needle adapter 614. Next, the needle is fixed in place by tightening the needle screw 616 over the needle adapter 614. Thereafter, the piston screw 612 is screwed into the thread 610, thereby pushing the piston 608 towards the needle and thus pushing the seed 102 together with some glycerin in the tube 602 into the needle. Next, the needle screw 616 is loosened and the needle is removed from the seed vial 600. In some embodiments, a silicone seal 644 is disposed in the receptacle 622 to prevent leakage from the tube 602. In some embodiments, the seed vial 600 contains approximately 10 milliliters of glycerin.

[0076] Note that instead of the threads 610 and the piston screw 612, any other suitable means can be used to push the piston 608 into the wide chamber 606.

[0077] Loading of the seed 102 into the applicator 200 and / or 500 using the seed vial 600 is through the distal end of the elongate hollow tube 202. Whether performed by the manufacturer of the applicator 200 and the applicator is pre-loaded and provided to the physician, loading from the distal end can be performed. By loading the seed 102 into the applicator 200 from the distal end, the distance the seed 102 needs to travel through the internal channel of the applicator and the potential damage caused by such passage are reduced. In some cases, the internal channel of the applicator can exceed 1 meter or even 1.5 meters, and when a seed passes through such a long and narrow channel, a significant percentage of the radionuclide on the seed can be rubbed off. Loading from the distal end is particularly important when the seed 102 provides alpha radiation, which is not normally covered by a substantial protective cover.

[0078] In the above description, the stylets of applicators 200 and 500 have two states. In the first state, the safety screw 220 holds the stylet in a retracted state, and the implant 100 is completely within the elongate tube 202. On the other hand, in the second state, after the safety screw 220 is removed, the stylet is pushed forward to extrude a part or all of the implant 100 out of the elongate tube 202. In some embodiments, it is desirable to define three or more states for the stylet 210. In the first state, the stylet is retracted, and the distal tip 102 of the elongate tube 202 is away from the end of the elongate tube, preventing radiation from the existing elongate tube 202. In the second state, the distal tip 102 within the elongate tube 202 is brought to the distal end of the elongate tube 202, enabling the physician to easily know the position of the distal tip. In the third state, the elongate tube 202 is retracted, and the stylet 210 is positioned at the most distal position with respect to the elongate tube 202. These states can be achieved by careful manual control by the physician, but in some embodiments, the applicator is provided with a mechanism to maintain the applicator in three different states. Although the description herein relates to three states, it should be noted that in some embodiments, the mechanism used to maintain the applicator in multiple states allows for more than four states.

[0079] FIG. 7A is a schematic view of an applicator 700 according to an embodiment of the present invention. FIG. 7B is a schematic view of the components of the applicator 700 according to an embodiment of the present invention. The applicator 700 includes a needle 702 having a proximal needle hub 704 that carries one or more seeds 102 (FIG. 1). The applicator 700 further includes a stylet 710 having a stylet hub 712. The needle hub 704 is configured to receive a safety screw 720 and defines a slot 730 that is used to fix the relative orientation of the stylet 710 within the needle 702 in a plurality of different states. Optionally, the slot 730 is reverse L-shaped. The stylet hub 712 defines one or more openings 734 that are configured to receive the safety screw 720. Optionally, the opening 734 has an internal thread configured to receive the safety screw 720. Alternatively, the opening 734 has any structure suitable for fixing the safety screw 720. As shown, the stylet hub 712 defines a plurality of openings 734 at different positions along the length of the stylet hub. The physician can select the use of one opening 734 through which the screw 720 is passed, depending on the number and / or length of the seeds 102 disposed within the needle 702.

[0080] In a first state, the safety screw 720 is disposed in the leg of the L-shaped slot 730 at the most proximal position of the needle hub 704. In this state, the seed 102 is disposed within the needle 702 away from the tip of the needle 702. In a second state, the screw 720 is disposed in the head of the L-shaped slot 730 at the most distal point of the slot. In the second state, the distal end of the stylet 710 is in a position to push the seed 102 to the tip of the needle 702. In a third state, the screw 720 is removed and the needle 702 is retracted towards the proximal end 738 of the stylet hub 712, leaving the seed 102 in the patient.

[0081] Figures 8A and 8B are schematic views of an external stopper 800 used to hold a stylet and a needle in a plurality of different relative states according to an embodiment of the present invention. The stopper 800 has a plurality of arm pairs designed to grip the stylet hub 802. The stopper 800 further has a lower slot 804 designed to receive the proximal notch 806 of the needle hub 808. As shown in Figure 8A, in the first state, the stylet hub 802 is held between the top arm pair 814 and the upper arm pair 812. In the first state, the stylet is prevented from moving distally and prematurely pushing one or more seeds 102 out of the needle. Further, when the needle is inserted into the patient's tissue, the stylet is prevented from moving proximally, i.e., rearward.

[0082] If it is desired to push the seed 102 to the distal tip of the needle, the stylet hub 802 is pushed out to the lower arm pair 816 from the recess defined by the arm pairs 812 and 814. Alternatively, the lower arm pair 816 is longer than the upper arm pair 812, and the stylet hub 802 moves easily from the first state to the second state. To move to the third state, the external stopper 800 can be removed from the needle hub 808 and the needle can be retracted onto the stylet.

[0083] Alternatively, the length of the stopper 800 from the lower slot 804 to the upper arm pair 814 is adjustable using the knob 820. In some embodiments, the stopper 800 includes two separate parts that are slidable relative to each other. The first part 822 has an outer frame that defines the lower slot 804, and the second part 824 has the arm pairs 812, 814, and 816. In some embodiments, the notches are defined for pre-set adjustable dimensions of the stopper 800 corresponding to different numbers of seeds 102 within the needle.

[0084] Figure 9 is a schematic view of a DaRT implant 190 according to another embodiment of the present invention. The DaRT implant 190 is similar to the implant 100 of FIG. 1, but includes a sealing ring at some or all ends of the seeds 102 to prevent the escape of radon near the seeds. As shown, the left seed 102 includes a sealing ring 194 that is fully attached to the seed itself. The ring 194 has an outer diameter configured to match the inner diameter of the elongated tube 202 and seals the space between the seed 102 and the tube 202. The seal prevents the escape of radon gas leaving the radionuclide on the seed 102 from the elongated tube 202. The right seed 102 includes a sealing ring 192 attached to a portion of the seed 102 and a portion of the delivery wire 104. Thus, the sealing ring 192 has two different inner diameters, an inner diameter that fits the delivery wire 104 and an inner diameter that fits the seed 102.

[0085] The sealing rings 192 and 194 are optionally made of silicone, such as USP Class VI silicone. Alternatively, the rings 192 and / or 194 are made of any other material suitable for sealing and preventing gas leakage. The sealing rings 192 and / or 194 are used instead of or in addition to the inlet seal 236, the distal seal 238, and / or the viscous liquid filling of the elongated tube 202.

[0086] Figure 10 is a schematic view of a button clip 950 according to an embodiment of the present invention. Optionally, the button clip 950 is used to secure the delivery wire instead of the buttons 406A and / or 406B. The button clip 950 has two semi - circles that are connected by a pivot and include notches to secure to each other. To secure the button clip 950 onto the delivery wire 104, the button clip is placed around the delivery wire 104 and the two semi - circles are pushed towards each other to secure the delivery wire 104 between the semi - circles.

[0087] It should be understood that the above-described methods and apparatuses are to be construed as including an apparatus for performing the method and a method of using the apparatus. The features and / or steps described with respect to one embodiment may be used with other embodiments, and it should be understood that not all embodiments of the present invention will have all of the features and / or steps shown in a particular figure or described with respect to one particular embodiment. The tasks are not necessarily performed in the order described.

[0088] Note that some of the above-described embodiments may not be essential to the present invention and may include details of structures, operations, or both structures and operations described by way of example. The structures and operations described herein can be replaced by equivalents that perform the same function, even if the structures or operations are different, as is known in the art. The above-described embodiments are cited by way of example, and the present invention is not limited to what is particularly shown and described above. Rather, the scope of the present invention includes both the various combinations and sub-combinations of the features described above, as well as variations and modifications thereof not disclosed in the prior art that would occur to one of ordinary skill in the art upon reading the above description. Accordingly, the scope of the present invention is limited only by the elements and limitations used in the claims, and the terms "comprising," "including," "having," and their conjugates, when used in the claims, mean "including but not necessarily limited to."

Claims

1. An apparatus for brachytherapy, comprising: a casing; one or more brachytherapy seeds within the casing, the seeds being seeds for extrusion from the casing for implantation into a patient, the casing being designed to enable extrusion of the seeds out of the casing, and the seeds carrying atoms that emit alpha rays of a radioactive element for radiotherapy; and a viscous liquid within the casing surrounding the one or more brachytherapy seeds; having each of the one or more brachytherapy seeds having a cylindrical shape including a length of at least 0.2 centimeters. An apparatus for brachytherapy, characterized by this.

2. The apparatus according to claim 1, characterized in that the casing has a needle.

3. The apparatus according to claim 1, characterized in that the viscous liquid has glycerin.

4. The apparatus according to claim 1, characterized in that the casing comprises a seed applicator having a tube adapted for insertion into the patient and a stylet within the tube.

5. The apparatus according to claim 4, characterized in that the casing has a hub at the proximal end of the elongated tube, the hub having an empty chamber configured to collect excess viscous liquid that occurs when the viscous liquid expands due to heat sterilization for the casing containing the viscous liquid from the elongated tube.

6. The apparatus according to claim 5, characterized in that the distal end of the hub connecting to the elongated tube has a funnel shape configured to enable the viscous liquid from the elongated tube entering the hub to return to the elongated tube.

7. The casing is a seed capsule, the seed capsule having a needle port at a first end for receiving a needle and a piston at a second end, the movement of the piston extruding the one or more brachytherapy seeds into the needle within the needle port, the apparatus of claim 1, wherein.

8. The needle port is configured to receive the needle in one direction and the movement of the piston causes the one or more brachytherapy seeds to enter the needle together with a portion of a viscous liquid, the apparatus of claim 7, wherein.

9. The atoms emitting the alpha rays are on the outer surface of the one or more brachytherapy seeds, the apparatus according to any one of claims 1-8, wherein.

10. The seed carries atoms emitting the alpha rays such that daughter nuclides from the seed can reach the patient's tissue, the apparatus according to any one of claims 1-8, wherein.

11. Each of the one or more brachytherapy seeds has a length of at least 0.5 centimeters in the extrusion direction of the seed, the apparatus according to any one of claims 1-8, wherein.

12. Each of the one or more brachytherapy seeds has a cylindrical tube with an outer diameter of at least 0.3 millimeters, the apparatus according to any one of claims 1-8, wherein.

13. The one or more brachytherapy seeds have seeds formed from a conductive material, the apparatus according to any one of claims 1-8, wherein.

14. The one or more brachytherapy seeds are configured to be removed from the patient after the treatment period of the radiotherapy treatment using the seeds, the apparatus according to any one of claims 1-8, wherein.

15. The viscous liquid is extruded out of the casing together with the seed and into the tumor. When the viscous liquid enters the tumor, the daughter nuclide of the atom that emits the alpha rays in the viscous liquid participates in the treatment of the brachytherapy of the tumor. The device according to any one of claims 1-8, characterized in that.

16. The viscous liquid can withstand sterilization at 160 degrees Celsius. The device according to any one of claims 1-8, characterized in that.

17. The casing is configured to carry one or more brachytherapy seeds in a manner that enables delivery of the seeds to the tumor by extruding the brachytherapy seeds from the distal end of the casing. The device according to any one of claims 1-8, characterized in that.

18. The casing defines a hollow tube. The device according to claim 17, characterized in that.

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