RU2808508C2 - Radioactive grain applicator - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: radioactive seed applicator includes the following components: a non-metallic elongate tube configured to be inserted into tissue; a sleeve at the proximal end of the tube; one or more radioactive beads carrying radioactive particles within the tube and a stylet configured to insert into the tube and push the one or more radioactive beads toward a distal end of the non-metallic extension tube when the non-metallic extension tube is in the tissue.

EFFECT: use of this invention will protect healthy tissues from undesirable radiation.

7 cl, 10 dwg

Description

TECHNICAL FIELD

The present invention relates generally to radiotherapy and, in particular, to methods of administering alpha particle grains to patients.

BACKGROUND OF THE ART

Brachytherapy is a powerful means of radiotherapy for certain types of tumors, including malignant ones. Proper delivery of beads with embedded particle emitters is important to the success of the therapy. Delivery must precisely position the grains within the tumor without prematurely exposing the patient's or other people's tissues to radioactive or other harmful substances.

US Patent Publication 2015/0375011, which is incorporated herein by reference in its entirety, discloses radioactive grain with bimetallic strips that "curl" when exposed to body temperature to lock the grain in place.

In many cases, brachytherapy devices are permanently implanted into the tumor and are not removed.

US Patent Publication 2003/0088144 issued to Terwilliger et al entitled "Improved Delivery System and Method for Interstitial Radiotherapy Using Hollow Beads", the disclosure of which is incorporated herein by reference in its entirety, proposes the use of a bioabsorbable filament of beads on which a plurality of hollow radioactive beads are mounted. tubular-shaped grains.

In other cases, brachytherapy devices are implanted for short periods of time, usually up to a few hours, called temporary brachytherapy.

US Pat. No. 9,272,160 to Kader et al., the disclosure of which is incorporated herein by reference in its entirety, discloses a brachytherapy thread with a cable that can be used to remove the thread.

US Patent Publication 2010/0249487, the disclosure of which is incorporated herein by reference in its entirety, discloses a flexible brachytherapy device to be implanted into the body with a tail portion extending beyond the body. The tail portion can be used to remove the brachytherapy device upon completion of therapy.

It has also been proposed to use a hollow needle and stylet to deliver grains to the site of implantation in the tumor.

US Patent Publication 2003/0191355 issued to Ferguson, the disclosure of which is incorporated herein by reference in its entirety, discloses the delivery of an assortment of beans into a needle using a stylet.

Patent Publication US 2008/0269540 issued to Lamoureux, the disclosure of which is incorporated herein by reference in its entirety, discloses the delivery of beans and optional spacers from a bean cartridge assembly through a hollow needle to the distal end of the hollow needle; and retracting the cannula while holding the stylet in place to thereby place the grains and optional spacers in the desired location. A reference is given to both the long and shorter stiletto.

US Pat. No. 6,752,753 to Hoskins et al., the disclosure of which is incorporated herein by reference in its entirety, discloses a needle and stylet for delivering beads to a tumor.

An important issue when using brachytherapy devices is protecting healthy tissue from unwanted radiation.

US Patent Publication 2014/0048729, the disclosure of which is incorporated herein by reference in its entirety, discloses a lightweight protective device to be worn on sensitive organs of the body.

US Patent Publication 2018/0082760, the disclosure of which is incorporated herein by reference in its entirety, discloses a transparent radiation shield.

DISCLOSURE OF THE INVENTION

In one aspect of some embodiments of the invention, a brachytherapy apparatus is disclosed, including a casing, one or more radioactive beads for implantation into a patient carrying atoms of a radioactive element for radiotherapy treatment within the casing, and a viscous liquid within the casing so as to prevent radiation from one or more of the beads from escaping from the casing. more radioactive grains from the casing. Optionally, the housing contains a needle. Alternatively, the housing contains a grain applicator including a tube adapted to be inserted into a patient and a stylet within the tube. As yet another alternative, the housing includes a grain capsule including a needle passage at a first end and a piston retaining one or more radioactive grains at a second end, wherein movement of the piston causes one or more radioactive grains to move into the needle into the needle passage.

Optionally, the viscous liquid contains glycerin. Optionally, the housing includes a sleeve at a proximal end of the elongate tube, the sleeve having an empty chamber configured to collect excess viscous fluid from the elongate tube when the viscous fluid expands due to heat sterilization. Optionally, the distal end of the sleeve connected to the elongate tube is shaped like a funnel configured to allow viscous fluid from the elongate tube entering the sleeve to return back to the elongate tube. Optionally, the needle passage is configured to receive the needle in an orientation such that one or more radioactive grains enter the needle along with a portion of the viscous liquid.

In addition, according to embodiments of the invention, a method of loading a needle with radioactive grains is provided, in which: gripping a needle having a sharp end for insertion into tissue so as to prevent movement of the needle, bringing the radioactive grain to a point adjacent to the tip of the needle, and pushing the radioactive grain into the needle , through the sharp tip.

Optionally, pushing the radioactive grain involves pushing a stylet that pushes the grain into the needle.

In addition, according to embodiments of the invention, there is provided a radioactive grain loading device comprising a central chamber for storing radioactive grain, a needle passage configured to lock the needle in an orientation such that the sharp tip of the needle is aligned with the radioactive grain in the central chamber, and a piston configured to pushing radioactive grain into a needle fixed in the needle passage.

Optionally, the central chamber additionally stores a viscous liquid that prevents radon released by the radioactive grain from escaping from the loading device. Optionally, the needle passage includes a screw that, when secured, secures the needle in the needle passage. Optionally, the device includes a piston screw, which, when rotated, pushes the piston towards the central chamber.

In addition, according to embodiments of the present invention, there is provided a radioactive grain applicator comprising a non-metallic elongate tube configured for insertion into tissue, a sleeve at the proximal end of the tube, one or more radioactive grains carrying radioactive particles within the tube, and a stylet configured for insertion into tube and pushing one or more radioactive beads to the distal end of the elongated tube.

Optionally, one or more radioactive grains carry alpha emitting particles. Optionally, one or more radioactive grains carry radium grains. Optionally, a non-metallic extension tube allows one or more radioactive grains to be visible in the ultrasound image of the applicator. Optionally, the non-metallic extension tube prevents the daughter nuclei of radioactive particles from escaping from the non-metallic extension tube. Optionally, one or more radioactive grains are located at a distance from the distal end of the non-metallic elongate tube of at least one centimeter. Optionally, the non-metallic extension tube contains Kapton.

In addition, according to embodiments of the present invention, there is provided a stopper for controlling movement of the stylet relative to a brachytherapy needle, comprising a housing frame, a first connector on the housing frame for gripping a brachytherapy needle hub, a second connector on the housing frame for gripping the stylet hub so as to prevent movement stylet in the distal direction; and a third connector on the housing frame for engaging the stylet sleeve so as to prevent movement of the stylet in either a proximal or distal direction.

Optionally, the first connector includes a slot for engaging the needle hub. Optionally, the second connector is configured to prevent distal movement of the stylet without preventing proximal movement of the stylet. Optionally, the second and third connectors are configured to engage the stylet sleeve at different axial positions relative to the needle. Optionally, the housing frame is configured to expand, changing the axial position in which the second and third connectors engage the stylet sleeve.

In addition, according to embodiments of the invention, there is provided a method of introducing radioactive grains into body tissue, which includes: providing a needle with radioactive grain therein, with a stylet inserted through the proximal end of the needle, and with a stopper holding the stylet sleeve in the first stylet connector, preventing both distal and proximal movement of the stylet relative to the needle, inserting the tip of the needle into the tumor, pushing the stylet sleeve from the first connector into the second connector, which prevents distal movement of the stylet sleeve in a different axial position of the stylet sleeve relative to the needle, different from the position in the first connector; the stopper is removed to allow the needle to be retracted proximally relative to the stylet, leaving the grain inside the tumor.

In addition, according to embodiments of the present invention, there is provided a brachytherapy implant comprising a hollow biocompatible wire, at least one tubular grain defining an internal channel mounted on the hollow biocompatible wire; and radioactive particles for radiotherapy treatment placed on the at least one tubular grain.

Optionally, a hollow biocompatible wire defines an internal channel with a diameter of less than 0.5 millimeters. Optionally, the biocompatible hollow wire is not biodegradable. Optionally, at least one tubular grain is located in the middle of the hollow biocompatible wire, at least 10 millimeters from both ends of the hollow biocompatible wire.

In addition, according to embodiments of the present invention, a method of introducing radioactive grain into body tissue is provided, in which: inserting a needle into body tissue through a first point until the tip of the needle comes out of the tissue at a second point, pushing out the distal end of a thread carrying one or more radioactive beads from the distal end of the needle, grasp the distal end of the thread, and withdraw the needle proximally from the tissue with the distal end of the thread grasped so that one or more radioactive beads remain in the tissue. Optionally, the method includes the step of pulling the distal end of the thread to adjust the position of one or more radioactive grains in the tissue. Optionally, gripping the distal end of the suture includes gripping with forceps. Optionally, inserting a needle into body tissue includes inserting a needle with a thread therein.

Brief description of drawings

FIG. 1 is a schematic view of a diffuse alpha emitter (DaRT) radiotherapy implant according to an embodiment of the invention; FIG.

fig. 2 is a schematic view of an applicator for delivering one or more grains to a patient site according to an embodiment of the invention;

fig. 3 is a flow chart of steps performed when delivering a DaRT implant to a tumor in a patient's arm according to an embodiment of the invention;

fig. 4A is a schematic view of an applicator during delivery of a DaRT implant to a tumor in a patient's arm according to an embodiment of the invention;

fig. 4B is a schematic view of an implant being secured in a patient's arm according to an embodiment of the invention;

fig. 5 is a schematic view of an applicator according to another embodiment of the invention;

fig. 6 is a schematic view of a bean container according to an embodiment of the invention;

fig. 7A is a schematic view of an applicator according to an embodiment of the invention;

fig. 7B is a schematic view of the components of the applicator of FIG. 7A according to an embodiment of the invention; And

fig. 8A and 8B are schematic views of an external stop used to hold the stylet and needle in a variety of different relative states, according to an embodiment of the invention;

FIG. 9 is a schematic view of a diffuse alpha emitter (DaRT) radiotherapy implant according to another embodiment of the invention; FIG.

Fig. 10 is a schematic view of a button clamp according to an embodiment of the invention.

IMPLEMENTATION OF THE INVENTION

An aspect of some embodiments of the invention relates to packaging radioactive beans in a package in which they are surrounded by a viscous liquid that prevents unwanted dispersion of particles from the beans. Optionally, the viscous liquid prevents the release of daughter nuclei, such as radon (Rn)-220, that have escaped from the packaging of the grains. The viscous liquid optionally does not boil during heat sterilization. In some embodiments, the viscous liquid comprises a biocompatible glycerol, optionally USP Class VI glycerin.

In some embodiments, the grains are preloaded into an elongated feed tube of the applicator device, and the elongated feed tube is filled with a viscous liquid. The viscous liquid collects the daughter nuclei released from the grains. When the grains are inserted into the tumor, a viscous fluid enters the tumor along with the grains, and the radioactive daughter nuclei in the viscous fluid are involved in brachytherapy treatment.

In some embodiments, the extension tube is a flexible tube that can be used to reach hard to reach areas with a rigid needle. In other embodiments, the elongated delivery tube includes a needle defining an internal delivery channel. Optionally, the grains are pre-stretched onto a delivery wire, such as a biocompatible thread or metal wire (eg, stainless steel, nitinol) in a tube.

The applicator device optionally includes, on the proximal side of the needle or other extended tube, a biocompatible sleeve for collecting viscous liquid during heat sterilization. The distal end of the biocompatible sleeve, where the sleeve connects to a needle or other extension tube, optionally has a funnel-shaped interior surface that allows for easy flow of viscous fluid back into the extension tube after heat sterilization is complete. During sterilization, the applicator is preferably held down by the distal end of the extension tube to minimize the amount of viscous liquid that exits the extension tube.

In other embodiments, the beans are placed in a sealed capsule filled with glycerin at a predetermined location designed to facilitate loading the beans into the needle. The capsule has a needle adapter head configured to receive a needle into the capsule in a position in which grain is loaded into the needle along with some glycerin. In this way, the radioactive grains are protected by a viscous liquid during delivery and loading into a needle or other applicator.

An aspect of some embodiments of the invention relates to loading radioactive beads into the needle applicator from the distal end of the needle (ie, the end inserted into the patient) rather than from the proximal end. Loading the needle from the distal end reduces the distance that the grains must travel in the internal channel of the applicator and the possible damage from such passage.

An aspect of some embodiments of the invention relates to a capsule for loading radioactive grains into an applicator. The capsule is configured to hold the radioactive grains in a closed chamber. Optionally, the first end of the chamber is configured to receive a needle, and the other end includes a piston configured to push grain into a needle extending through the first end.

An aspect of some embodiments relates to an applicator device having a non-metallic tube configured to transfer one or more alpha-emitting radioactive beads into human tissue. The non-metallic tube is configured to prevent alpha radiation from escaping from the tube and thus prevents the radiation from being prematurely emitted to healthy tissue. The use of a non-metallic tube allows the use of imaging techniques such as ultrasound to precisely position the grains while they are inside the tube and prevents the emission of alpha radiation into healthy tissue. Optionally, the grains are spaced from the distal end of the tube at a distance of at least 3 millimeters, at least 5 millimeters, or even at least 9 millimeters to prevent radiation leakage through the tip of the tube.

Optionally, the applicator tube is removed from the patient's tissue after confirming the location of the grains in the tumor, for example, using ultrasound or computed tomography (CT). Removal of the tube activates brachytherapy treatment as the alpha particles and daughter granule nuclei can now reach the patient's tissue. The clear extension tube optionally contains a polymer such as Kapton. Alternatively, the tube is formed from any other suitable biocompatible polymer that is resistant to the heat and/or radiation used for sterilization, such as biocompatible polyetheretherketone (PEEK).

In some embodiments, the applicator device includes a mechanism for controlling the arrangement of beans in the elongate tube relative to a distal end of the tube. Optionally, the grains are initially 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 escaping from the distal end of the tube. After checking the location of the distal end of the tube relative to the tumor, an applicator is used to bring the grains to the distal end of the elongated tube. The extended tube is then retracted proximally, leaving the grains in their place in the patient.

An aspect of some embodiments relates to a stopper for controlling movement of the stylet relative to the elongate applicator tube, which has at least one condition that limits or prevents both proximal and distal movement. Optionally, the stopper further has at least one state in which the stopper restricts only distal movement and not proximal movement.

An aspect of some embodiments of the invention relates to a brachytherapy implant including one or more tubular-shaped beads carrying particle emitters mounted on a delivery wire. In some embodiments, the feed wire comprises a hollow tube. Using a hollow tube as a feed wire allows the wire to be simply secured by pressing the wire so that the parts of the wire that are not pressed protrude outward.

An aspect of some embodiments relates to a method of implanting radioactive seeds into a patient. The method involves inserting a delivery thread carrying grains into a body organ into a needle that enters the organ from one side and exits from the other side. The physician grasps the distal end of the delivery thread and adjusts the location of the grains by moving the distal end of the delivery thread.

In some embodiments, a needle is inserted into an organ with the delivery thread enclosed within the needle. Alternatively, the thread is inserted into the needle after the needle has been inserted into the organ. For example, the delivery thread may be inserted within a flexible tube into a separate needle previously inserted into a body organ.

1 shows a schematic view of a diffuse alpha emitter (DaRT) radiation therapy implant 100 according to an embodiment of the invention. The implant 100 includes a delivery wire 104 with one or more radioactive beads 102 secured therein. Each grain 102 contains a cylindrical tube with an internal tunnel through which a feed wire 104 passes. While in FIG. 1 the feed wire 104 is shown with two grains 102, the feed wire 104 may be threaded through any suitable number of grains, including through a single grain 102 or multiple grains 102, perhaps more than three or even more than five, in depending on the needs of the individual patient. The supply wire 104 can optionally be flexible so that, in portions along its length not covered by the beads 102, it can bend as needed to fit the patient. Attaching the beans to the wire 104 allows multiple beads 102 to be introduced into the patient at the same time. The delivery wire 104 can be used to secure the beads 102 in place in the patient, and/or can be used to remove the beads 102 from the patient after a treatment session.

Each grain 102 optionally has a length of at least 0.2 centimeters, 0.5 centimeters, or even at least 0.8 centimeters. Optionally, 102 grit is shorter than 2.1 centimeters or even shorter than 1.5 or 1.2 centimeters. In some embodiments, grain 102 is about 1 centimeter in length. The grain optionally has an outer diameter of at least 0.3 millimeters, at least 0.5 mm, or even at least 0.6 mm. In some embodiments, grain 102 has an outer diameter of about 0.7 millimeters, while in other embodiments, grain 102 has an outer diameter of 0.35 millimeters. The inner diameter of the grain 102 is optionally greater than 0.2 millimeters, greater than 0.4 millimeters, or even greater than 0.5 millimeters. In some embodiments, the internal diameter of grain 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 grains 102 optionally have a length that is at least 2 times, at least 5 times, or even at least ten times their outer diameter. Grain 102 optionally contains stainless steel, such as 316LVM stainless steel, titanium, nitinol, and/or any other suitable biocompatible conductive material.

The feed wire 104 has an outer diameter approximately equal to the inner diameter of the grain 102. In some embodiments, the outer diameter of the wire 104 is smaller than the inner diameter of the grain 102 such that the wire 104 moves freely within the grain. In other embodiments, the diameter of the wire 104 is substantially equal to the internal diameter of the grain 102 such that the grain 102 does not move relative to the wire 104 without the application of at least a predetermined force. The difference between the inner diameter of the grains 102 and the outer diameter of the wire 104 is optionally greater than 5 microns, greater than 15 microns, or even greater than 25 microns. The difference between the inner diameter of the grains 102 and the outer diameter of the feed wire 104 is preferably less than 60 microns, less than 40 microns, or even less than 30 microns.

Wire 104 optionally contains a metal, such as nitinol, or stainless steel, such as 316LVM stainless steel. Alternatively, wire 104 contains a biocompatible filament compound. For example, the feed wire 104 may comprise a polymer filament such as polypropylene, polyester, polytetrafluoroethylene (PTFE) and/or PEEK. The feed wire 104 is optionally made of biodegradable material. Alternatively, the delivery wire 104 is not biodegradable, so the delivery wire 104 can be used to remove the grains 102 from the patient after the treatment interval. The treatment interval may be at least a week, at least a month, or even at least three months.

Optionally, the grains 102 are attached to the feed wire 104 to prevent them from sliding along the feed wire 104 using any suitable method known in the art. In some embodiments, the feed wire 104 contains a biocompatible polymer filament that is inflated to prevent the grains 102 from sliding along the feed wire 104. Alternatively or additionally, the grains 102 are secured to the feed wire 104 by deforming the feed wire 104, such as by forming a knot at the ends of the grains 102.

In some embodiments, the feed wire 104 is formed from a material that expands when heated. After the feed wire 104 is inserted into one or more grains 102, it is heated so that the wire is attached to the grains. In some embodiments, the delivery wire 104 includes a hollow tube that can be easily deformed by a clinician so that the delivery wire 104 can be secured, as explained below.

The grains 102 on the feed wire 104 may be spaced apart or adjacent to each other, with very little space between the ends of adjacent grains 102 (eg, less than 0.5 millimeter or even less than 0.05 millimeter).

In some embodiments, one or more grains 102 are mounted in the middle of the feed wire 104 such that the free ends of the feed wire 104 remain on either side of the grain 102. Optionally, the ends of the feed wire 104 not covered by the grains 102 have a length equal to at least at least 5 millimeters, at least 10 millimeters or even at least 20 millimeters. Thus, the physician can use both ends of the feed wire 104 to adjust the position of the beads 102 within the tumor and/or to secure the beads 102 within the tumor. In addition, after the treatment period, the delivery wire 104 can be used to remove the grains 102 from the patient.

In other embodiments, one or more beads 102 are mounted on the end of a delivery wire 104 that serves as a tang for adjusting and/or securing bead locations and/or removing beads after treatment is completed.

Grain 102 is loaded with particles of a radioactive substance. Optionally, the radioactive material contains alpha-emitting atoms on the outer surface of the grain 102. The particles are secured to the grain using any method known in the art, including any of the methods described in US Pat. No. 8,834,837 to Kelson et al. and entitled: "Method and apparatus for radiotherapy", and publication of patent US 2009/0136422 issued to Kelson. et al. and entitled “Radioactive Surface Source and Method for Producing The Same,” which are incorporated herein by reference in their entirety. In some embodiments, the grains carry radium-223 or radium-224 particles. Alternatively, the grains carry other suitable particles such as radon-219, radon-220 or thorium-228. Optionally, grain 102 contains up to 5 μCi and/or up to 185 kBq of radium 224. However, it should be noted that in other embodiments, grain 102 is loaded with other amounts of radioactive substances or other radioactive substances that emit other particles, such as beta and/or gamma particles.

In fig. 2 shows a schematic view of an applicator 200 for delivering one or more beans 102 to a patient site according to an embodiment of the invention. The applicator 200 includes an elongate hollow tube 202 configured to receive the implant 100 and having a proximal tube sleeve 204 that serves as a handle. The applicator 200 further includes a stylet 210 configured to be inserted into an elongate hollow tube 202. The stylet 210 has a proximal stylet sleeve 212 that at least partially fits into a hollow channel within the tube sleeve 204. Optionally, a safety screw 220 is used to secure a hole 206 in the tube sleeve 204 to a corresponding hole 216 in the stylet sleeve 212 and thereby secure the distal end of the stylet 210 at a predetermined location within the tube sleeve 204 or at the proximal portion of the elongate hollow tube 202. Security a cap 222 optionally covers the elongated tube 202 during manipulation.

In some embodiments, the elongated hollow tube 202 includes a rigid needle, such as a stainless steel needle. Alternatively, the elongate hollow tube 202 includes a flexible tube, such as a Kapton tube, such as a clear Kapton tube, allowing a physician to view the grains 102 within the elongate hollow tube 202. Optionally, in accordance with this alternative, in order to insert the tube 202 into a patient, a separate hollow needle of any desired shape (eg, straight, curved) is inserted into the patient, and tubing 202 is inserted into the separate needle.

The delivery wire 104 is optionally fully contained within the extension tube 202. In order to insert one or more grains 102 on the delivery wire 104 into the patient, the extension tube 202 is brought to the desired implant site. The safety screw 220 is then removed and the stylet 210 is advanced so as to push the distal portion of the feed wire 104 out of the distal end of the elongated tube 202. Using the stylet 210 to push the feed wire 104 out of the elongated hollow tube 202 allows the grains 102 to be positioned at a distance from the distal end. extension tube 202 during transportation and before actual use so as to prevent unwanted radiation leakage. Optionally, during transport, the distal end of the outermost grain 102 in 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.

The stylet 210 in some embodiments is shorter than the needle 202 such that the distal end of the stylet 210 does not reach the distal end of the needle 202. Optionally, the stylet 210 has a length suitable for pushing the delivery wire 104 in a distal direction to the point where the small distal portion of the delivery wire 104 protrudes from the needle 202. The stylet 210 optionally has sufficient length to push the proximal end of the delivery wire 104 to the point at which the distal end of the delivery wire 104 protrudes slightly from the needle 202. The extent to which the delivery wire 104 protrudes from the needle 202 after it is pushed with a 210 stylet, optionally less than 20 millimeters, less than 10 millimeters or even less than 8 millimeters. The length of the stylet 210 is optionally slightly greater than the difference between the length of the needle 202 and the shortest feed wire 104 considered to be placed in the needle 104. Alternatively, the stylet 210 has a length suitable for pushing the grain 102 to the distal end of the needle 102, for example, having a length , equal to the difference between the lengths of the needle 202 and the grain 102. The use of a short stylet is especially useful in cases where the needle is inserted into a body organ when it exits from the opposite side of the organ. In such cases, the physician has easy access to the distal end of the delivery wire 104, which protrudes from the needle 202, and thus can adjust the position of the grain 102 without the use of the stylet 210.

In some embodiments, the applicator 200 is provided with an inlet seal 236 at the proximal end of the elongate tube 202 or at a distal portion of the tube sleeve 204 adjacent the proximal end of the elongate tube 202. The inlet seal 236 prevents radon gas traveling through the elongate tube 202 from escaping proximally from the elongate tube 202. Optionally, inlet seal 236 comprises a Wilson seal that retains its sealing properties even when stylet 210 passes through inlet seal 236 into elongate tube 202. Alternatively, inlet seal 236 comprises stretched foil. Additionally, as an alternative, the input seal 236 comprises any other suitable seal, such as any suitable seal described in GM Hofz, "Overview of Drive Shaft Seal Techniques for Expanded Space Missions," National Aeronautics and Space Administration, December 15 1972, incorporated herein by reference. The applicator 200 optionally also includes a distal seal 238 at the distal end of the elongated tube 202. The distal seal 238 includes, for example, a beeswax plug or biocompatible foil that prevents radon gas from escaping the distal end of the elongated tube 202. Alternatively, any other suitable material may be used. a sealing material that can be easily removed when the implant 100 is to exit the elongated tube 202.

In fig. 3 shows a flowchart of the steps performed when delivering a DaRT implant to a tumor in a patient's arm 402 (FIG. 4) according to an embodiment of the invention. The implantation process begins by removing (302) the protective cap 222 from the elongated hollow applicator tube 202 (FIG. 2). An elongated hollow tube 202 is inserted (304) into the patient's arm where the tumor is located. In embodiments in which the elongated 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 an elongated hollow tube 202 is inserted into the separate needle.

When it is determined (306) that the distal end of the elongate hollow tube 202 is positioned correctly, the locking of the stylet 210 relative to the elongated hollow tube 202 is released (308), for example, by removing the safety screw 220. Then, while holding the tube sleeve 204, the stylet sleeve 212 is pushed (310 ) in a distal direction such that the distal end of the stylet 210 pushes the implant 100 distally and thereby forces the distal end of the delivery wire 104 to exit the elongated tube 202.

In fig. 4A shows a schematic view of the applicator 200 during delivery of a DaRT implant to a tumor in a patient's arm 402 according to an embodiment of the invention. 4A shows the applicator 200 after the stylet sleeve 212 is pushed (310) distally.

The clinician grasps (312) the distal portion of the delivery wire 104, for example, with forceps, and the applicator 200 is removed proximally from the patient, leaving the delivery wire 104 and one or more beans 102 thereon in the patient's hand 402. The delivery wire 104 is moved as necessary to adjust (314) its position, and when positioned correctly, the delivery wire 104 is secured (316) in place.

In some embodiments, securing (316) is achieved using locking buttons on both sides. Any suitable locking buttons may be used, such as those described in US Pat. No. 2,075,508 to Davidson entitled “Thread Locker,” the disclosure of which is incorporated herein by reference in its entirety. Optionally, after placing the locking button on the end of the wire 104, the wire is deformed adjacent to the button to keep the button pressed against the patient. As mentioned above, in some embodiments, wire 104 comprises a hollow tube. In these embodiments, the wire 104 is optionally deformed by being pressed against the wire using a pliers or any other suitable tool, causing the sides of the wire that were not pressed to bulge outward.

In fig. 4B shows a schematic view of the attachment of the implant 100 (FIG. 1) in a patient's arm 402 according to an embodiment of the invention. In fig. 4B shows the first button 406A already positioned on the proximal end of the delivery wire 104 and the second button 406B ready for installation. To secure the button, pliers 404 are used to press the clamp, which locks the button in place. Alternatively, a button that serves as a clamp is used, as described below with reference to FIG. 10, and pliers 404 are used to press the button. Additionally, as an alternative, the feed wire 104 itself is deformed to lock the button in place. In embodiments in which the feed wire 104 is hollow, pressure on the feed wire deforms the wire such that the wire flexes at points where pressure is applied and bulges out at points where pressure is not applied. This prevents the button 406A from falling off the feed wire 104. In other embodiments, securing is achieved by bending the feed wire 104 laterally. In embodiments in which the feed wire 104 contains a flexible thread, fastening is optionally achieved by knotting the thread.

Alternatively or in addition to using the inlet seal 236 and/or the distal seal 238 to prevent radiation from escaping from the grains 102 during manipulation, the hollow tube 202 is filled with a viscous liquid to prevent the radon particles from escaping. In addition, the viscous liquid creates a vacuum effect that allows grain 102 that has partially exited the hollow tube 202 to be sucked back into the hollow tube 202 if it is determined that the grain is not properly positioned. This vacuum effect is particularly useful in embodiments in which the hollow tube 202 is metal and other means described herein for precise positioning of the grains 102 are not used. Optionally, after determining that the tip of the needle and the grain 102 are properly positioned (306) using available means, the physician pushes the stylet 210 the amount necessary to partially release the grain from the distal end of the tube 202. The position of the grains 102 is then checked and a decision is made whether to continue to push the beans out of the extension tube 202 or to suck the beans 102 back into the extension tube 202 and adjust the position of the end of the tube 202 to release the beans 102 more accurately.

The viscous liquid optionally contains a biocompatible material that can withstand sterilization at temperatures of approximately 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 includes 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 sleeve 204 defines an internal empty chamber designed to collect excess viscous fluid from the elongate hollow tube 202 when the viscous fluid expands due to heat sterilization. Optionally, the distal end of the proximal tube sleeve 204 connecting to the elongate tube 202 has a funnel shape 226 configured to allow viscous fluid from entering the elongate tube sleeve 204 to return to the elongate tube 202.

Glycerin is optionally loaded into the elongate hollow tube 202 from the distal end of the elongate hollow tube 202. A syringe containing glycerin is optionally connected to the distal end of the elongate hollow tube 202, and glycerin from the syringe is pushed into the tube 202.

The viscous liquid may fill the elongate hollow tube 202 completely or only a portion of the tube 202 surrounding the grains 102. Optionally, the viscous liquid covers at least 10 millimeters on each side of the grains 102.

In fig. 5 shows a schematic view of an applicator 500 according to another embodiment of the invention. Similar to applicator 200, 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 needle hub 506 within the needle hub 504. Applicator 500 differs from applicator 200 in that its stylet is longer and should be approximately equal in length to needle 502, allowing the clinician to expel the entire contents of needle 502 from the needle. Thus, the applicator 500 can be used to introduce one or more beans to a patient in locations where the needle 502 does not exit the patient from the opposite side and does not allow the beans 102 and/or feed wire 104 to be pulled from the opposite side. In some embodiments, the applicator 500 includes a depth adapter 510 that is used to adjust the length of the needle 502 inserted into the patient. Optionally, the depth is adjusted by rotating the depth adapter 510 about the thread on the outer surface of the needle hub 504.

The applicator 500 is used, in some embodiments, in conjunction with a template specifying the position at which the grains are to be inserted, as disclosed, for example, in Patent Publication US 2017/0319871 to Pitman entitled: "Coordinate Needle Fixation System for Brachytherapy" and/or US Patent Publication No. 2014/0296612 issued to Schwartz entitled: "Brachytherapy Assistive Device", the disclosures of which are incorporated herein by reference in their entirety.

In some embodiments, applicators 200 and/or 500 are provided to physicians preloaded with one or more grains 102. 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 beans 102 into a needle. The applicator needle 200 and/or 500 is optionally supplied without pre-loaded beans 102, and the clinician loads the desired amount of beans 102 into the needle. Alternatively, the needle comes preloaded with a minimum number of grains, such as one grain, and the clinician loads one or more additional grains as needed.

In fig. 6 shows a schematic view of a bean container 600 according to an embodiment of the invention. The grain container 600 includes a tube 602 defining on one side a narrow central chamber 604 configured to hold radioactive grains 102 and on the other side a wide chamber 606 configured to receive a piston 608 carrying a stylet 642 configured to push the grain 102 held in a narrow chamber 604, into a needle. An O-ring 620 is optionally positioned toward the end of the piston 608 such that when the piston 608 is pushed into the chamber 606, fluid from the wide chamber 606 is forced into the narrow chamber 604. The outer side of the tube 602 on the side of the wide chamber 606 optionally defines a thread 610 that matches the piston screw 612, which may be screwed onto the threads 610 so as to push the piston 608 into the chamber 606. The bean container 600 further includes a needle adapter 614 and a needle screw 616 that serve as a passage for receiving a needle into the bean loading device 600. The needle adapter 614 includes on one side a hole 622 with an internal thread that screws onto a corresponding thread 624 on the tube 602. At the opposite end, the needle adapter 614 includes a resilient member 628 having an external thread 618. When the internal screw of the needle screw 616 screws onto the external thread 618 needle adapter 614, the elastic member 628 is pressed inward and narrows the inner needle channel 630 of the needle adapter 614. When the needle is in the needle channel 630, pressure on the elastic element 628 prevents the needle from moving.

The tube 602 is optionally filled with glycerin, which prevents radiation from the beans 102 from escaping from the bean container 600. The bean container 600 is provided with a piston screw 612 threaded only onto a limited end portion of thread 610 and a needle screw 616 threaded only onto a limited end portion of thread 618. In order to load grain 102 from bean container 600 into the needle, the needle is inserted through needle screw 616 and needle adapter 614 into the narrow chamber 604 of tube 602. The needle is then secured in place by tightening needle screw 616 over needle adapter 614. The piston screw 612 is then screwed onto the threads 610 to push the piston 608 towards the needle and thus push the grain 102 along with some glycerin in the tube 602 into the needle. The needle screw 616 is then released and the needle is removed from the bean container 600. In some embodiments, a silicone seal 644 is placed in the opening 622 to prevent leakage from the tube 602. In some embodiments, the bean container 600 contains about 10 milliliters of glycerin.

It should be noted that in lieu of threading 610 and piston screw 612, any other suitable means may be used to push piston 608 into wide chamber 606.

Loading of beans 102 into applicator 200 and/or 500 using bean container 600 is accomplished through the distal end of the elongated hollow tube 202. Loading from the distal end may also be accomplished where loading is performed by the manufacturer of applicator 200 and the applicator is provided to the physician preloaded. Loading the grains 102 into the applicator 200 from the distal end reduces the distance that the grains 102 must travel in the internal channel of the applicator and the possible damage from such passage. It should be noted that in some cases the applicator has an internal channel more than a meter or even more than 1.5 meters long, and passing the beans through a narrow channel of this length can result in the removal of a significant percentage of the radioactive nuclides on the beans. Distal end loading is especially important when the grains 102 emit alpha radiation and are not typically covered by a durable protective coating.

In the above description, the stylet of applicators 200 and 500 has two states. In the first condition, the safety screw 220 holds the stylet retracted and the implant 100 is completely contained in the extension tube 202, while in the second condition, after the safety screw 220 is removed, the stylet is advanced to push part or all of the implant 101 out of the extension tube 202 In some embodiments, it is necessary to define three or more states for the stylet 210. In the first state, the stylet is retracted and the distal grain 102 in the elongated tube 202 is spaced from the end of the elongated tube 202 to prevent radiation from escaping from the elongated tube 202. In the second state, the distal grain 102 inside the elongated tube 202 is brought to the distal end of the elongated tube 202, allowing the physician to easily know the position of the distal grain. In the third state, the elongate tube 202 is retracted such that the stylet 210 is positioned at its outermost position relative to the elongate tube 202. Although these states can be achieved by a physician through careful manual control, in some embodiments the applicator is provided with a mechanism to maintain the applicator in three different states. It should be noted that although the present description refers to three states, in some embodiments, the mechanisms used to maintain the applicator in multiple states allow for more than three states.

In fig. 7a shows a schematic view of an applicator 700 according to an embodiment of the invention. In fig. 7B shows a schematic view of the components of an applicator 700 according to an embodiment of the invention. The applicator 700 includes a needle 702 that carries one or more grains 102 (FIG. 1), and has a proximal needle hub 704. The applicator 700 further includes a stylet 710 having a stylet sleeve 712. The needle hub 704 defines a slot 730 configured to receive a safety screw 720 used to secure the relative orientation of the stylet 710 within the needle 702 in a variety of different states. The slot 730 may have an inverted L-shape. Stylet sleeve 712 defines one or more holes 734 configured to receive a locking screw 720. Optionally, the holes 734 are internally threaded to receive a screw 720. Alternatively, the holes 734 are of any other structure suitable for a locking screw 720. As shown. , the stylet sleeve 712 defines a plurality of holes 734 at different positions along the length of the stylet sleeve. The physician may choose to use one of the holes 734 for passage of the screw 720 in accordance with the number and/or length of grains 102 to be placed in the needle 702.

In the first condition, the screw 720 is placed in the leg of the L-shaped slot 730 in the most proximal position on the needle hub 704. In this state, the grains 102 are located inside the needle 702, at a distance from the tip of the needle 702. In the second state, the screw 720 is located in the head of the L-shaped slot 730 at the outermost point of the slot. In the second condition, the distal end of the stylet 710 is in a position that pushes the grains 102 toward the tip of the needle 702. In the third condition, the screw 720 is removed and the needle 702 is retracted toward the proximal end 738 of the stylet hub 712, leaving the grains 102 in the patient.

In fig. 8A and 8B show schematic views of an external stopper 800 used to hold the stylet and needle in a variety of different relative states, according to an embodiment of the invention. The stopper 800 includes a plurality of pairs of levers for engaging the stylet sleeve 802. The stopper 800 further includes a lower slot 804 configured to receive a proximal notch 806 of the needle hub 808. In the first state, the stylet sleeve 802 is held between the upper pair of arms 814 and the upper pair of arms 812, as shown in FIG. 8A. In the first condition, the stylet cannot move distally and prematurely push one or more grains 102 out of the needle. In addition, the stylet is prevented from moving proximally, that is, backwards, when the needle is inserted into the patient's tissue.

If the grain 102 needs to be pushed toward the distal end of the needle, the stylet sleeve 802 is pushed out of the recess formed by the pairs of arms 812 and 814 onto the lower pair of arms 816. Optionally, the lower pair of arms 816 is longer than the upper pair of arms 812 so that the stylet bush 802 is easily moved out of the first state to the second state. To enter the third state, the outer stopper 800 is removed from the needle hub 808, allowing the needle to be retracted onto the stylet.

Optionally, the length of the stopper 800 from the lower slot 804 to the upper pair of arms 814 is adjustable using a knob 820. In some embodiments, the stopper 800 includes two separate parts that are slidable relative to each other. The first portion 822 includes an outer frame that defines the bottom slot 804, and the second portion 824 includes pairs of arms 812, 814, and 816. In some embodiments, the notches are defined for predetermined adjustable stopper 800 sizes corresponding to different numbers of grains 102 in the needle.

FIG. 9 is a schematic illustration of a DaRT implant 190 according to another embodiment of the invention. DaRT implant 190 is similar to implant 100 of FIG. 1, but includes O-rings on the edges of some or all of the grains 102 that prevent radon from leaking from the grain area. As shown, the grain 102 on the left includes o-rings 194 that are fully seated on the grain itself. The rings 194 have an outer diameter configured to match the inner diameter of the elongated tube 202 so as to seal the space between the grains 102 and the tube 202. The seal prevents radon gas from releasing radioactive nuclides on the grain 102 from the elongated tube 202. The right grain 102 includes o-rings 192 that are mounted partly on the grain 102 and partly on the feed wire 104. Accordingly, the o-rings 192 have two different inner radii: one corresponding to the feed wire 104 and the other to the grain 102.

O-rings 192 and 194 optionally contain silicone, such as USP Class VI silicone. Alternatively, rings 192 and/or 194 contain any other material suitable for sealing and preventing gas leakage. O-rings 192 and/or 194 are used instead of or in addition to inlet seal 236, distal seal 238, and/or filling elongate tube 202 with viscous fluid.

FIG. 10 shows a schematic view of a button clip 950 according to an embodiment of the invention. Button clamp 950 is optionally used to secure the feed wire in place of buttons 406A and/or 406B. The button clip 950 includes two semicircles that are hinged and include recesses that lock into each other. In order to secure the button clamp 950 to the feed wire 104, the button clamp is placed around the feed wire 104, and the two halves are slid towards each other to be secured by the feed wire 104 between the halves.

It should be understood that the methods and apparatus described above should be interpreted as including an apparatus for performing the methods and methods for using the apparatus. It should be understood that the features and/or steps described with respect to one embodiment may sometimes be used with other embodiments, and that not all embodiments of the invention have all the features and/or steps shown in a particular drawing or described with respect to one specific embodiments. The tasks are not necessarily performed in the exact order described.

It should be noted that some of the embodiments described above may include structure, actions, or details of structures and actions that may not be essential to the invention and are described as examples. The structure and operations described herein may be replaced by equivalents that perform the same function, even if the structure or actions differ, as is known in the art. The embodiments described above are given as an example, and the present invention is not limited to what has been specifically shown and described above. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described above, as well as variations and modifications thereof, which may become apparent to those skilled in the art upon reading the foregoing description, and which are not disclosed in the prior art. Therefore, the scope of the invention is limited only by the elements and limitations used in the claims, where the terms "comprise", "include", "have" and their conjugates mean, when used in the claims, "to include but not necessarily be limited thereto".

Claims (11)

1. Radioactive grain applicator containing: a non-metallic tube configured to be inserted into tissue; a sleeve at the proximal end of the tube; one or more radioactive grains carrying radioactive particles inside the tube; and a stylet configured to insert into the tube and push one or more radioactive beads toward a distal end of the non-metallic tube when the non-metallic tube is in the tissue. 2. The radioactive grain applicator according to claim 1, wherein the one or more radioactive grains carry alpha emitting particles. 3. The radioactive grain applicator according to claim 1, wherein the one or more radioactive grains carry radium particles. 4. The radioactive grain applicator according to any one of claims 1 to 3, wherein the non-metallic tube allows one or more radioactive grains to be visible in an ultrasonic image of the applicator. 5. The radioactive grain applicator according to any one of claims 1-4, in which the non-metallic tube prevents the daughter nuclei of radioactive particles from leaving the non-metallic tube. 6. The radioactive grain applicator according to any one of claims 1 to 5, wherein one or more radioactive grains is located at a distance from the distal end of the non-metallic tube equal to at least one centimeter. 7. The radioactive grain applicator according to any one of claims 1 to 6, wherein the non-metallic tube comprises a flexible tube.