Radiation therapy applicator with vertical or angled radial distribution

Abstract

A device for implanting radiotherapeutic seeds in a tumor. The device includes a delivery tube having a distal end designed to enter the tumor and defining an internal passage, and an elongated applicator carrying one or more radiotherapeutic seeds, each seed having a length of at least 1 millimeter, the applicator passing through the internal passage of the delivery tube. When the distal end of the elongated applicator is proximate to the distal end of the delivery tube, the distal end of the elongated applicator assumes an angle relative to the axis of the delivery tube such that the seeds ejected from the elongated applicator enter the tumor at an angle relative to the axis of the delivery tube.

Description

Invention Field

[0001] The present invention relates generally to radiotherapy, and more particularly to methods and apparatus for distributing alpha-emitting radioisotope sources in tumors. Background of the Invention

[0003] Ionizing radiation is commonly used to treat certain types of tumors, including malignant cancerous tumors, by destroying the tumor cells.

[0004] For example, the diffuse alpha emitter radiotherapy (DaRT) described in Kelson’s U.S. Patent 8,834,837 extends the therapeutic range of alpha radiation by using radium-223 or radium-224 atoms, which produce several chains of radioactive decay.

[0005] For tumor treatment to be effective, the DaRT seeds used in the treatment should be implanted throughout the tumor at small intervals (e.g., less than 5 millimeters). Some tumors are easily accessible to doctors from the outside for seed implantation, while others are located in internal organs.

[0006] U.S. Patent Publication 2022 / 0142500 by Greenburg et al. describes an integrated, multifunctional endoscopic tool including a needle that can be used to implant a seed source for brachytherapy.

[0007] Glioblastoma (“GBM”) is a cancerous tumor located in the brain. Due to its proximity to core nerves and brain cells, as well as its neural connections to the spinal cord, it has become a particularly difficult form of cancer to treat, with no effective treatment available that can harm or kill the patient. Therefore, GBM is one of the deadliest forms of cancer, with virtually no available treatment options and a bleak prognosis for survival.

[0008] U.S. Patent Publication 2013 / 0204124 by Duindam et al. describes a flexible needle that can be used to deliver radioactive seed sources to internal locations that are difficult to access via a straight path. Invention Overview

[0010] Embodiments of the present invention relate to implanting multiple radiotherapy seed sources into a tumor through a single insertion port for introducing a seed source applicator into the tumor.

[0011] Therefore, according to embodiments of the present invention, an apparatus for implanting radiotherapy seed sources in a tumor is provided, the apparatus comprising: a delivery tube having a distal end designed to enter the tumor and defining an internal channel; and an elongated applicator carrying one or more radiotherapy seed sources, each radiotherapy seed source having a length of at least 1 mm, the applicator passing through the internal channel of the delivery tube, wherein, when the distal end of the elongated applicator approaches the distal end of the delivery tube, the distal end of the elongated applicator forms an angle relative to the axis of the delivery tube, such that the seed sources ejected from the elongated applicator enter the tumor at an angle relative to the axis of the delivery tube.

[0012] Optionally, the device includes a core needle within an elongated applicator, the core needle being designed to advance one or more radiotherapy seeds relative to the elongated applicator when the distal end of the applicator is within the tumor, thereby ejecting the seeds from the elongated tube into the tumor. Optionally, the device includes a core needle handle configured to precisely advance the core needle relative to the elongated applicator by a distance equal to the length of the seeds at the distal end of the elongated applicator. Optionally, the core needle handle is configured to advance the core needle while keeping the elongated applicator stationary. Alternatively, the core needle handle is configured to keep the core needle stationary while retracting the elongated applicator.

[0013] Optionally, the distal end is configured to eject the seed source from the elongated applicator at an angle of at least 5° relative to the axis of the delivery tube. Optionally, the distal end is configured to eject the seed source from the elongated applicator at an angle of at least 30° relative to the axis of the delivery tube. Optionally, the distal end is configured to eject the seed source from the elongated applicator at an angle of at least 45° relative to the axis of the delivery tube. Optionally, the distal end is configured to eject the seed source from the elongated applicator at an angle of less than 25° relative to the axis of the delivery tube. Optionally, the distal end is configured to eject the seed source from the elongated applicator at an angle of less than 15° relative to the axis of the elongated tube.

[0014] In some embodiments, the elongated applicator includes a nitinol tube. Optionally, the delivery tube is configured to rotate within a tumor. Optionally, the device includes a rotation mechanism configured to rotate the delivery tube within the tumor by a predetermined angle. Optionally, an inner hollow channel is configured to carry and eject seed sources, the inner hollow channel having a length of at least 5 mm. Optionally, the distal end of the elongated tube is configured to form an angled bend relative to the axis of the elongated tube when no external force is applied. Optionally, the delivery tube includes a side window toward its distal end, and wherein the applicator is configured to eject one or more radiotherapy seed sources through the side window. Optionally, the delivery tube includes two concentric tubes that rotate relative to each other to open and close the window. Optionally, the delivery tube includes a bevel near the window, the bevel causing the distal end of the elongated applicator tube to form an angle relative to the axis of the elongated tube. Optionally, the elongated applicator carries at least three seed sources or even at least five seed sources.

[0015] According to an embodiment of the present invention, a method for inserting seed sources into a tumor is also provided, the method comprising: inserting a delivery tube into a first depth in the tumor; while the delivery tube is at the first depth, ejecting a plurality of seed sources from the delivery tube into the tumor, wherein each of the plurality of seed sources is ejected at an angle relative to the axis of the delivery tube, and wherein the plurality of seed sources are ejected at at least two different radial angles; and moving the delivery tube to a second depth in the tumor and ejecting one or more seed sources from the delivery tube into the tumor at the second depth.

[0016] Optionally, ejecting multiple seed sources includes ejecting the seed sources at an angle of at least 10° relative to the axis of the delivery tube. Optionally, ejecting multiple seed sources includes rotating the delivery device while the delivery tube is at a first depth to eject the seed sources at different radial angles. Optionally, ejecting one or more seed sources from the delivery tube into the tumor at a second depth includes ejecting seed sources shorter than those at the first depth. Optionally, ejecting the same number of seed sources from both the first and second depths. Optionally, ejecting the seed sources at the first depth at a radial angle different from that at the second depth.

[0017] According to embodiments of the present invention, a method for planning radiotherapy for a tumor is also provided, the method comprising: acquiring images of the tumor; determining the type of the tumor; determining the coverage area of ​​the entire tumor by means of one or more cylindrical regions, the cylindrical regions having a diameter not greater than a predetermined maximum diameter corresponding to the determined tumor type; for each of the one or more cylindrical regions, selecting multiple seed sources and selecting multiple seed sources located in each of the layers, the multiple seed sources needing to provide a sufficient radiation dose to each point in the cylindrical region, wherein each layer includes multiple seed sources to be implanted from the delivery tube when the distal end of the delivery tube is located at a single point; and proposing a plan for implanting seed sources in the tumor in response to the determined cylindrical regions, the number of seed source layers, and the number of seed sources in each of the layers. Optionally, these layers are conical layers. Optionally, the predetermined maximum diameter is at least 10 mm. Brief description of the attached diagram

[0019] Figure 1 This is a schematic cross-sectional view of a medical probe for implanting a radiotherapy seed source into a patient, according to an embodiment of the present invention.

[0020] Figure 2 According to an embodiment of the present invention Figure 1 A schematic diagram of the distal end of the probe;

[0021] Figure 3 This is a schematic diagram of a system for embedding seed sources into tumors according to an embodiment of the present invention;

[0022] Figures 4A to 4C These are, respectively, three-dimensional, exploded, and cross-sectional views of the rotating mechanism according to an embodiment of the present invention;

[0023] Figure 5 This is a schematic diagram of the seed source layout according to an embodiment of the present invention;

[0024] Figure 6 This is a graph showing the estimated alpha particle radiation dose reaching a cross-section of a glioblastoma (GBM) tumor according to an embodiment of the present invention, wherein the seed source is similar to... Figure 5 The layout of the implant is inserted into a glioblastoma (GBM) tumor;

[0025] Figure 7 This is a method for placing seed sources in a tumor according to an embodiment of the present invention;

[0026] Figure 8 This is a schematic diagram of a pre-loaded applicator during delivery and before use, according to an embodiment of the present invention.

[0027] Figure 9 This is a schematic diagram of the distal sleeve (hub) of the applicator during delivery, according to an embodiment of the present invention; and

[0028] Figure 10 This is a cross-section of a delivery tube system according to another embodiment of the present invention. Detailed Implementation

[0029] One aspect of some embodiments of the present invention relates to a method of implanting radiotherapy seed sources into a tumor, wherein the distal end of an applicator is inserted into one or more pivot points within a patient's body, and a plurality of seed sources are dispensed at different angles from each of the one or more pivot points. In some embodiments, the plurality of elongated seed sources dispensed at different angles from a single pivot point comprises seed sources dispensed at at least three different radial angles, at least four different radial angles, or even at least six different radial angles, forming a cone, flower, or sun shape. The seed sources are uniformly or non-uniformly distributed around the single pivot point, for example, depending on the shape of the tumor.

[0030] Implanting an elongated seed source at different angles from a single pivot point results in varying distances between the proximal end of the seed source near the single point and the distal end far from the single point. This difference in distance between different portions of the seed source is undesirable because the destructive range of radiation from the seed source decreases sharply with the extent of radiation from the seed source. However, the applicant has determined that a sun-shaped arrangement can provide sufficient radiation to destroy the tumor, and the advantage of simplifying seed source implantation by reducing the number of insertion points for the delivery tube within the patient outweighs the irregularity of the radiation distribution. Minimizing the number of insertion points is particularly important for glioblastoma tumors in the brain, a fragile tissue where minimizing hemorrhage is crucial. Nevertheless, embodiments of the present invention may be advantageous in treating other tumors requiring percutaneous seed source implantation, such as lung, pancreatic, and liver tumors.

[0031] One aspect of some embodiments of the present invention relates to a probe for implanting radioactive seed sources into a tumor. The probe includes an external delivery tube whose distal end is introduced into the tumor, and an elongated applicator carrying one or more radiotherapy seed sources, the elongated applicator passing through an inner channel of the external delivery tube. The probe is designed such that the distal end of the elongated applicator dispenses the seed sources at an angle (i.e., an angle other than zero, such as at least 2° or even at least 5°) relative to the axis of the external delivery tube. Furthermore, the probe is designed to allow for changing the radial angle at which the elongated applicator dispenses the seed sources without removing the external delivery tube from the tumor. In some embodiments, the external delivery tube is rotated within the patient to change the radial angle at which the seed sources are emitted. Optionally, the elongated applicator rotates with the external delivery tube. Alternatively, the elongated applicator does not rotate with the external delivery tube, but is angled relative to the external delivery tube due to an internal slope or protrusion in the delivery tube, making rotation of the applicator unnecessary. Alternatively, the external delivery tube remains stationary, and the elongated applicator rotates. In some embodiments, the applicator has a large rotation angle of at least 180°, at least 270°, at least 300°, or even up to a full 360°. The applicator optionally allows an operator to radially distribute multiple seed sources from a single insertion depth, with each seed source distributed at a different radial angle. The operator can optionally adjust the angle between the seed sources such that the seed sources are uniformly or non-uniformly distributed around the applicator. When the applicator is inserted or removed, the operator can potentially distribute seed sources at multiple depths along the insertion axis, rather than repeatedly inserting the applicator to distribute seed sources directly below the applicator. Therefore, various aspects of the present invention allow for minimally invasive application of radiotherapy seed sources in GBM or other tumors and provide alternative delivery mechanisms to existing devices.

[0032] Figure 1 This is a schematic cross-sectional view of a medical probe 100 for implanting a radiotherapy seed source into a patient according to an embodiment of the present invention. The probe 100 includes an external delivery tube 102 and an internal drug delivery device 106, the internal drug delivery device 106 passing through the inner channel of the delivery tube 102.

[0033] The internal delivery device 106 defines an internal channel carrying a plurality of seed sources 112 at its distal end, which will be delivered to the tumor. Proximal to the seed sources 112, the internal channel of the delivery device 106 carries a core needle 114 for pushing the seed sources 112 into the tumor.

[0034] The external delivery tube 102 has a side window 110 at its distal end, through which the distal end 118 of the applicator 106 exits the external delivery tube 102 and / or ejects the seed source 112 into the tumor. In some embodiments, the delivery tube 102 is formed by two concentric tubes (outer tube 132 and inner tube 134), each tube having an opening for the window 110. The window 110 is open when tubes 132 and 134 are aligned, and closed when tubes 132 and 134 are not aligned. At its proximal end, the outer tube 132 includes a sleeve 104. Similarly, the inner tube 134 has a sleeve 128 at its proximal end. The window 110 is opened and closed by rotating the sleeve 128 relative to the sleeve 104. In some embodiments, an O-ring 144 seals the connection between the sleeve 104 and the sleeve 128.

[0035] In some embodiments, the applicator 106 has a sleeve 124 at its proximal end, and the sleeve 124 is configured to engage with a sleeve 128. Optionally, the sleeve 124 is designed with an inner chamber that engages with the sleeve 128 in a first state, in which the distal end of the applicator 106 exits the window 110. In a second state, the sleeve 124 is retracted such that the distal lip 146 of the sleeve 124 engages with the proximal region of the sleeve 128. Optionally, in the second state, rotation of the sleeve 124 causes the sleeve 128 to rotate together with the inner tube 134. Thus, a physician can open and close the window 110 by rotating the sleeve 124. In some embodiments, a suitable notch (not shown) prevents the sleeve 124 from moving into the first state unless the window 110 is open.

[0036] As discussed below, sleeve 124 is shown having a silicone sheet 142 that seals the proximal end of applicator 106 during delivery prior to use.

[0037] In some embodiments, the external delivery tube 102 includes a biopsy needle. In other embodiments, the external delivery tube 102 includes a probe carrying a camera, such as an endoscope or bronchoscope. In still other embodiments, the external delivery tube 102 includes any other suitable medical probe. The external delivery tube 102 includes materials that are clinically safe to insert into the body organ to which it is intended. For example, when the medical probe 100 is configured for the treatment of glioblastoma, the external delivery tube 102 is designed for safe insertion into brain tissue. The probe 100 can be used for other cancers, such as hepatocellular carcinoma. In some embodiments, the external delivery tube 102 includes a straight, rigid tube. Alternatively, the external delivery tube 102 is flexible to pass through blood vessels or other curved paths within a patient's body. According to this alternative, the axis of the external delivery tube 102 is considered to be the axis of a segment near the distal end of the external delivery tube 102.

[0038] The elongated applicator 106 includes a biocompatible tube formed of a material that is optionally flexible or otherwise pre-configured into a specific shape to achieve flexibility. In some embodiments, the elongated applicator 106 includes a polyimide, such as Kapton.

[0039] The elongated applicator 106 and the external delivery tube 102 optionally have a length of at least 250 mm (such as 300 mm). The elongated applicator 106 optionally has an outer diameter of about 1.25 mm and an inner diameter of about 0.85 mm. The delivery tube 102 optionally has a diameter between 1.5 mm and 2.5 mm, for example between 1.8 mm and 2.2 mm, such as about 2.1 mm. Note that other sizes may be used depending on the task to be performed.

[0040] In some embodiments, the core needle 114 has different levels of rigidity along its length. In the proximal portion of the core needle 114, the core needle has high rigidity sufficient to push the seed source 112 without collapsing. The distal portion of the core needle 114 has lower rigidity, so it can conform to turns in the applicator 106.

[0041] Figure 2 This is a schematic diagram of the distal end 200 of the probe 100 according to an embodiment of the present invention. Optionally, to allow the applicator 106 to exit the window 110, the delivery tube 102 includes a tilted portion 136 that radially pushes the applicator 106 at a desired angle when the applicator 106 is pushed distally. As an alternative to the tilted portion 136, the applicator 106 is configured with shape memory to have a tilt at a desired angle when not restricted by the delivery tube 102. According to an alternative, when the window 110 is open, the distal end of the applicator 106 presents a predetermined angle and exits the window 110 by rotating the tubes 132 and 134 for alignment. In some embodiments, the elongated applicator 106 comprises nitinol or any other material with shape memory properties. In other embodiments, a flexible guide wire is used to bend the distal portion of the delivery tube 102 near the window 110.

[0042] As shown in the figure, the distal end 118 of the applicator 106 forms a relatively small angle relative to the axis of the delivery tube 102, such as less than 25°, less than 20°, less than 15°, less than 10°, or even less than 5°. This relatively small angle has the advantage of requiring a relatively small turn in the applicator 106 to achieve this angle, so that the seed source 112 can easily slide within the applicator 106 when the applicator turns.

[0043] In other embodiments, the distal end 118 of the applicator 106 forms a large angle relative to the delivery tube 102, such as at least 30°, at least 40°, at least 50°, or even at least 60°. In some embodiments, the distal end 118 forms an angle of approximately 90° with the axis of the applicator 106 (e.g., between 85° and 95°). Using this large angle achieves coverage of a larger area around the delivery tube 102, thereby reducing the number of different entry points for the delivery tube 102 into the tumor, ensuring that radiation from the seed source 112 covers the entire tumor. In some embodiments, to simplify the passage of the seed source 112 through the applicator 106, particularly when the angle between the applicator 106 and the delivery tube 102 is large, the seed source 112 is flexible, for example, made of a flexible material or made thin.

[0044] Figure 3 This is a schematic diagram of a system 300 for embedding seed material into a tumor according to an embodiment of the present invention. System 300 includes a medical probe 100, such as... Figure 1 As shown, the medical probe 100 includes a delivery tube 102 and a drug applicator 106 therein. Additionally, the system 300 optionally includes a needle guide tube 302, with a proximal portion of a needle 114 extending beyond the drug applicator 106. The distal end of the needle guide tube 302 includes an interface 304 connected to a sleeve 124 of the drug applicator 106. At its proximal end, the needle guide tube 302 is connected to a needle handle 306, which includes a push mechanism 308 connected to the needle 114 for controllably pushing the needle 114 by a desired amount. Optionally, the handle 306 defines a notch 310, the notches 310 being separated from each other by the length of a single seed source 112. The push mechanism 308 optionally includes a lever (not shown) mounted in the notch 310. To eject the seed source 112, the lever is pulled out of its corresponding notch 310 using the handle 312 on the push mechanism 308, and then the push mechanism 308 is pushed forward until the lever falls into the next notch 310. In other embodiments, any other suitable mechanism is used to control the length of movement of the push mechanism 308 of a single seed source, or otherwise control the ejection of the seed source 112. In some embodiments, all seed sources 112 used together in a single applicator 106 have the same length, so the notches 310 are separated by equal distances matching the seed source lengths. Alternatively, the applicator 106 may include seed sources of different lengths, and the notches are spaced accordingly at different intervals matching the lengths of the seed sources to be ejected.

[0045] In some embodiments, instead of the push mechanism 308 pushing the core needle 114, the handle 306 includes a mechanism for retracting the applicator 106 to a precise length (e.g., the length of a single seed source) while keeping the core needle 114 fixed.

[0046] The system 300 may optionally include a clamp 332 mounted on the delivery tube 102 and fastened to it by a screw 334. A rotation mechanism 320 is mounted on the clamp 332 and is used to rotate the delivery tube 102 with the applicator 106 within the tumor.

[0047] Figures 4A to 4C The figures shown are three-dimensional, exploded, and cross-sectional views of a rotating mechanism 320 according to an embodiment of the present invention. The rotating mechanism 320 includes a fixed base 342 designed to be attached directly or indirectly to a patient. For example, when the system 300 is used to treat a head tumor, the fixed base 342 can be attached to a head frame. An adjustable base 344 is placed within the fixed base 342 and fixed relative to the fixed base 342 by a locating pin 346 located in an inner channel on a side portion 348 of the fixed base 342. A movable handle 350 is used to slide the locating pin 346 and push the locating pin 346 into two or more notches 352 (in...). Figure 4B In one of the notches (designated 352A and 352B), the notch 352 is designed to receive a locating pin 346 in such a way that it locks the adjustable base 344 to the fixed base 342. In some embodiments, the adjustable base 344 defines a groove 366 that extends along a radial region connecting the notch 352. A screw 368 within the fixed base 342 is optionally locked in the groove 366, restricting relative rotation of the bases 342 and 344 to a region between two or more notches 352.

[0048] The rotating mechanism 320 also includes a rotating handle 354, which defines an inner shaft designed to be mounted on a clamp 332. The rotating handle 354 optionally clamps the clamp 332 between an upper stop 356 and an indexing rod 358. The indexing rod 358 is optionally designed to be located within an adjustable base 344 and rotates with the handle 354. Figure 4C As shown, the indexing rod 358 is optionally secured to the rotating handle 354 by screws 364. In some embodiments, the indexing rod 358 has a radially oriented bore 360 ​​into which the seed source 112 will be inserted. Optionally, a corresponding spherical plunger 362 located in the adjustable base 344 is mounted into the bore 360 ​​and stops rotation of the handle 354 at the desired radial angle. As an alternative to the spherical plunger 362, any other suitable mechanism can be used to stop rotation of the handle 354 at the desired radial angle.

[0049] Optionally, the adjustable base 344 has markings, such as numbers, that guide the user when rotating the handle 354.

[0050] In some embodiments, the elongated applicator 106 rotates together with the outer delivery tube 102, for example, due to the connection of their sleeves. Alternatively, the elongated applicator 106 does not rotate with the outer delivery tube, but rather presents an angle relative to the outer delivery tube due to the inwardly inclined portion 136 or protrusion in the delivery tube, making rotation of the applicator 106 unnecessary. Furthermore, alternatively, instead of rotating the outer delivery tube 102, a rotating mechanism 320 is mounted on the elongated applicator 106.

[0051] Note that the rotation mechanism 320 provided herein is merely an example, and any other suitable mechanism for rotating the delivery tube 102 and / or the elongated applicator 106 can be used. For example, instead of manual rotation of the handle 354, a stepper motor can be used to perform the desired amount of rotation. In some embodiments, the stepper motor is calculated by a processor, which precisely controls the rotation based on instructions from the operator. Optionally, the operator indicates the number of seed sources to be implanted in each layer, and the processor calculates and implements the rotation angle accordingly.

[0052] Figure 5 This is a schematic diagram of the layout 400 of the seed source 112 according to an embodiment of the present invention. As shown, the seed source 112 is implanted into the tumor from the delivery tube 102, located in a plurality of conical layers 402 (in Figure 5 (Ref. 402A, 402B, and 402C). Each seed source layer forms a conical or sun-shaped configuration. The seed sources 112 of each layer 402 are optionally ejected from the delivery tube 102 at the same depth within the tumor at different rotation angles of the window 110. Each layer 402 optionally includes a seed source 112 having at least four radial angles, at least six radial angles, at least eight radial angles, at least ten radial angles, or even at least twelve radial angles. Thus, the angle between any two radial angles of the ejected seed source 112 is less than 60°, less than 45°, less than 36°, or even less than 30°. Optionally, the distance between the distal ends 410 of the seed sources 112 of a single layer 402 is chosen such that the distance between each point in the tumor and the radionuclide on one of the seed sources 112 is within a sufficiently short distance. The radial angles of the ejected seed sources 112 are optionally uniformly spaced at approximately the same angle. Alternatively, for example in irregular tumors, the seed source spacing may be non-uniform. Optionally, the seed source 112 in each layer spans 360° around the delivery tube 102. Alternatively, the delivery tube 102 is inserted into or near the edge of the tumor, and the seed source 112 is ejected into the tumor at an angle span suitable for embedding the seed source 112 into the tumor.

[0053] In some embodiments, seed sources 112 in different layers 402 are emitted at the same radial angle; for example, seed sources 112A, 112B, and 112C are emitted at the same radial angle. Alternatively, seed sources 112 in adjacent layers 402 are emitted at different radial angles to provide better tumor coverage. In one embodiment according to this alternative, the seed source of layer 402B is positioned at a radial angle halfway between the radial angles of the seed sources in layers 402A and 402C. This can be optionally achieved by moving the locating pin 346 between notches 352A and 352B.

[0054] The distance between layers 402 may be less than 8 mm, less than 5 mm, or even less than 4 mm. In some embodiments, the distance between adjacent layers 402 is such that the distance between the projection of the distal end of the seed source 112 of one layer (e.g., 402B) onto the axis defined by the delivery tube 102 and the projection of the proximal end of the seed source 112 of the adjacent layer (e.g., 402C) onto that axis is less than a predetermined length. The predetermined length may be less than 4 mm, less than 3 mm, less than 2 mm, less than 1 mm, or even negative, such that the layers 402 overlap.

[0055] In some embodiments, all seed sources 112 have the same length and are ejected at the same angle. Alternatively, seed sources for different layers may have different lengths and / or be ejected at different angles. For example, two different layers 402 may be generated from delivery tubes 102 at the same depth in the tumor with different ejection angles and possibly different seed source lengths.

[0056] Optionally, the layout of the seed source 112 is selected such that the distance between any point in the cylindrical region centered on the axis of the delivery tube 102 and the distance between any point and one of the seed sources 112 does not exceed a predetermined maximum distance. The maximum distance may optionally be no greater than 2 mm, no greater than 1.8 mm, or even no greater than 1.6 mm.

[0057] In one embodiment, each layer includes seven seed sources, each seed source being 10 mm in length and embedded at a 15° angle. The tapered shape of each layer may optionally be present on its narrower side (seed source 112 in...). Figure 5The upper point of the delivery tube 102 has a diameter of less than 4 mm, less than 3.6 mm, or less than 3.2 mm (e.g., about 3 mm). The proximal end of the seed source is optionally spaced at least 0.3 mm or even at least 0.5 mm from the outer circumference of the delivery tube 102 to prevent the seed source 112 from obstructing movement of the delivery tube 102. The proximal end of the seed source is optionally spaced at less than 1 mm or even less than 0.8 mm from the outer circumference of the delivery tube 102 to prevent a gap with a small radiation dose near the inlet axis of the delivery tube 102. On its wider side, the cone may optionally have a diameter greater than 5 mm or greater than 6 mm (e.g., about 7 mm). In this embodiment, for a single insertion of the delivery tube 102 into the patient, covering a cylinder with a radius of 5.5, the maximum distance from each point in the cylinder to the nearest seed source is 2 mm.

[0058] Figure 6 This is a graph showing the estimated alpha particle radiation dose reaching a cross-section of a glioblastoma (GBM) tumor according to an embodiment of the present invention, wherein the seed source is similar to... Figure 5 The layout 400 was implanted into a glioblastoma (GBM) tumor. This diagram was created assuming a seed source length of 6 microcuries per centimeter and a desorption probability of 45%, which corresponds to a radon release rate of 2.7 microcuries per centimeter. The layout is assumed to consist of six conical layers 402, each containing eight 10-millimeter seed sources, and the conical layers 402 are spaced 4 millimeters apart.

[0059] As can be seen in the figure, this arrangement achieves a dose greater than approximately 20 g / L in a region approximately 11 mm in diameter, centered on an axis 450 around the delivery tube 102 for implanting the seed source into this arrangement. In the lower portion of this region, there is a circumferential region 452 surrounding a low-dose region 454. To avoid this configuration, the lowest layer may optionally include a shorter seed source, for example, shorter than 6 mm or shorter than 4 mm. Alternatively or additionally, one or more additional seed sources 112 may be implanted in region 454 along axis 450.

[0060] Figure 7This is a method for placing seed source 112 into a tumor according to an embodiment of the present invention. The method begins by inserting (502) the distal end of delivery tube 102 into a first point (referred to herein as the first pivot point) in the tumor. Then (504) window 110 is opened, and seed source 112 is ejected (506) through window 110 into the tumor. Then, the distal end of applicator 106 is retracted into delivery tube 102, and delivery tube 102 with applicator 106 is rotated (508) to different radial angles without changing the depth of delivery tube 102 in the tumor. Another seed source is optionally ejected (510) from the first pivot point at a different radial angle. Optionally, the rotation (508) and ejection (510) of seed source 112 are repeated until (512) a sufficient number of seed sources 112 are ejected from the first pivot point. Then, the delivery tube 102 is moved (516) to an additional pivot point, and the rotation (508) and ejection (506, 510) of the seed source 112 are repeated. Depending on the size of the tumor (514), the delivery tube 102 is further moved (516) to an additional pivot point, and an additional layer 402 of the seed source 112 is arranged in the tumor. The radial angles may be evenly spaced at approximately the same angle, or they may be unevenly spaced. The pivot points may optionally all be located on a straight line at different depths of insertion of the delivery tube 102 into the tumor.

[0061] In some embodiments, the same number of seed sources 112 are ejected into the tumor in the same radial layout across all layers 402. Alternatively, different layouts and / or different numbers of seed sources 112 may be used at different depths, for example, depending on the size and / or shape of the tumor. In some embodiments, the movement from a first depth to a subsequent depth is in the insertion direction, such that the first depth is closest to the entry point of the delivery tube 102 into the tumor. Alternatively, the movement from the first depth to a subsequent depth is in the retraction direction, and the first depth is selected to be furthest from the entry point of the delivery tube 102 into the tumor.

[0062] exist Figure 7 In this method, when all the seed sources 112 in the applicator 106 have been ejected, the applicator 106 may optionally be removed from the delivery tube 102 and replaced by a different applicator 106 loaded with additional seed sources 112. Replacement may also be performed when the delivery tube 102 is within the tumor. If the length of the seed sources 112 loaded in the replacement applicator 106 differs from the length of the seed sources 112 previously used with the removed applicator 106, the handle 306 may also optionally be replaced with a handle 306 having slots 310 spaced apart in a manner that matches the length of the seed sources 112 in the replacement applicator 106.

[0063] In some embodiments, after the seed source 112 is ejected, one or more seed sources 112 are implanted along the axis of the delivery tube 102. These embodiments are optionally used when the tumor region occupied by the delivery tube 102 is kept at a distance from the radially implanted seed sources 112 during implantation of the seed sources 112. However, it is noted that in some cases, after the delivery tube 102 is removed, the seed sources 112 implanted in the tumor move posteriorly with the tumor tissue to occupy the area where the delivery tube 102 was located. In this case, the axial seed sources 112 may not be necessary.

[0064] In some embodiments, before implanting the seed source into the tumor, a layout plan is prepared, for example by the processor, which includes the intended location of the seed source within the tumor. Optionally, the dose reaching each point in the tumor is estimated to verify that a sufficient dose will reach each point in the tumor. In some embodiments, a region of the tumor is determined, for example from medical images surrounding the tumor, and that region is determined accordingly. Depending on the type of tumor, such as as discussed in PCT application PCT / IB2022 / 055322 entitled “Activity Levels for Diffusing Alpha-Emitter Radiation Therapy,” which is incorporated herein by reference in its entirety, the dimensions of the cylinder to be covered by the implantable seed source layer are determined. Subsequently, a minimum number of cylindrical regions and corresponding insertion points for the delivery tube 102 are determined. For each cylindrical region, the length of the region is determined, and the number of layers covering the region is selected accordingly. Thus, the processor presents instructions to the user regarding the seed source to be implanted.

[0065] Each seed source 112 optionally has a length of at least 0.1 cm, 0.2 cm, 0.5 cm, or even at least 0.8 cm. Optionally, the seed source 112 is shorter than 2.1 cm, or even shorter than 1.5 cm or 1.2 cm. In some embodiments, the seed source 112 has a length of approximately 1 cm. The seed sources may all have the same length, or different seed sources may have different lengths. In some embodiments, instead of using seed sources of different lengths, multiple seed sources are ejected at a single radial angle in the direction of greater tumor size.

[0066] Seed source 112 may optionally have an outer diameter of at least 0.3 mm, at least 0.5 mm, or even at least 0.6 mm. In some embodiments, seed source 112 has an outer diameter of approximately 0.7 mm, while in other embodiments, seed source 112 has an outer diameter of 0.35 mm. The inner diameter of seed source 112 may optionally be greater than 0.2 mm, greater than 0.4 mm, or even greater than 0.5 mm. In some embodiments, the inner diameter of seed source 112 is less than 2 mm, less than 1 mm, or even less than 0.5 mm. In some embodiments, the inner diameter is approximately 0.25 mm or 0.4 mm. Seed sources 112 may all have the same diameter, or different seed sources may have different diameters.

[0067] The tubular seed source 112 optionally has a length of at least 2, at least 5, or even at least 10 times its outer diameter. The seed source 112 optionally comprises stainless steel, such as 316LVM stainless steel, titanium, nitinol, zirconium oxide, alumina, and / or any other suitable biocompatible material. In some embodiments, the seed source 112 is formed of a conductive material to allow for the attachment of a radionuclide to the seed source using methods requiring a conductive seed source. Alternatively, a non-conductive material is used for the seed source 112, and other suitable methods are used to attach the radionuclide to the seed source, such as a suitable thin coating.

[0068] Seed source 112 is loaded with particles of radioactive material. Optionally, the radioactive material comprises alpha-emitting atoms on the outer surface of seed source 112. Particles are attached to the seed source using any method known in the art, including any method described in U.S. Patent 8,834,837 entitled "Method and Device for Radiotherapy" by Kelson et al., and U.S. Patent Publication 2009 / 0136422 entitled "Radioactive Surface Source and a Method for Producing the Same" by Kelson et al., the contents of which are incorporated herein by reference in their entirety. In some embodiments, the seed source carries radium-223 or radium-224 particles. Alternatively, the seed source carries other suitable particles, such as radon-219, radon-220, or thorium-228. In one particular embodiment, seed source 112 contains up to 5 μCi and / or up to 185 kBq of radium-224. In other embodiments, seed source 112 carries a higher level of activity. However, it should be noted that in yet other embodiments, seed source 112 is loaded with other amounts of radioactive material or other radioactive material that radiates other particles (such as beta and / or gamma particles).

[0069] Figure 8This is a schematic diagram of a pre-loaded applicator 106 during delivery and before use, according to an embodiment of the invention. During delivery, the applicator 106 is pre-loaded with a radioactive seed source 112. To prevent leakage of the radionuclide from the applicator 106, the applicator 106 may optionally be sealed at its proximal and distal ends, as discussed below.

[0070] At the proximal end of the applicator 106, the sleeve 124 includes a silicone sheet 142 that seals the proximal end of the applicator 106. Figure 1 At its distal end, the applicator 106 is connected to the extension tube 602. Figure 9 The extension tube 602 extends beyond the area including the seed source 112 and is configured to be filled with a liquid that captures radionuclides from the seed source and prevents them from leaving the applicator 106. The extension tube 602 is covered by the distal sleeve 604 of the applicator 106.

[0071] In some embodiments, a liquid is supplied from the manufacturing site to a pre-loaded applicator 106, the liquid capturing radionuclides already present in the applicator 106. These embodiments can be used, for example, when sterilization is performed using gamma rays, which do not require the high temperatures required to boil the liquid. In other embodiments, to allow sterilization at temperatures above the liquid's boiling point, the liquid is introduced into the applicator 106 immediately before the removal of the seal and immediately before the commencement of the method for implanting the seed source 112.

[0072] Figure 9 This is a schematic diagram of a distal sleeve 604 according to an embodiment of the present invention, wherein liquid is introduced immediately prior to the implantation procedure. The distal sleeve 604 includes a tubular connection sleeve 608 connecting the applicator 106 to an extension tube 602. The distal sleeve 604 also includes a seed source stop 610, which prevents the seed source 112 from leaving the applicator 106. The seed source stop 610 optionally includes a suitable heat-resistant material, such as polyetheretherketone (also known as PEEK). The distal sleeve 604 also includes a distal silicone sheet 612 held between two screws 614 and 616, sealing the applicator 106 at the distal end of the distal sleeve 604. Finally, the distal sleeve 604 includes a syringe sleeve 618.

[0073] In preparation for use, a syringe (not shown) containing a suitable liquid for capturing radionuclides is attached to the syringe sleeve 618, and the core needle 114 is retracted from the applicator 106 by a suitable range (e.g., 40 mm) to reduce the pressure in the applicator 106. Liquid from the syringe is then filled into the extension tube 602, and due to the low pressure in the applicator 106, it is filled from the extension tube 602 in a manner that surrounds the seed source 112. Subsequently, the extension tube 602 is detached from the applicator 106, for example by cutting it in a cutting groove 620 of the distal sleeve 604, and the distal sleeve 604 is removed from the applicator 106. The liquid surrounding the seed source 112 within the applicator 106 prevents radon from escaping from the applicator 106 and also holds the seed source 112 in place and prevents unwanted movement.

[0074] In some embodiments, the liquid is a biocompatible viscous liquid, such as glycerol. In other embodiments, such as when treating tumors in the brain, the liquid comprises a brain tissue-compatible material, such as saline. Optionally, the extension tube 602 has a length of at least 5 mm or at least 8 mm (e.g., 10 mm). The liquid in the extension tube 6020y has a volume of about 1 microliter.

[0075] Figure 10 This is a cross-section of a delivery tube system 700 according to another embodiment of the present invention. (And...) Figure 1 Unlike the delivery tube 102, which has a side window 110 through which the distal end of the applicator 106 exits, in the delivery tube system 700, the applicator 106 exits through the distal end. The delivery tube system 700 includes a delivery tube 702 and a cannula 704 located within an inner channel of the delivery tube 702.

[0076] In use, the delivery system 700 is first inserted into the patient, with the cannula 704 inside the delivery tube 702. After reaching the desired pivot point for seed source 112 placement, the cannula 704 is removed from the delivery tube 702, and the applicator 106 is inserted into the delivery tube 702 to implant the seed source at an angle to the delivery tube 702, forming a conical arrangement of the seed source. One or more seed sources 112 can be implanted along the axis before or after the angled implantation of the seed source 112, using different applicators without turning.

[0077] in conclusion

[0078] While the foregoing description relates to the use of biocompatible materials, the invention is not limited to such materials, and such non-biocompatible materials may be used in medically permissible cases, such as for components that do not come into contact with sensitive patient tissues.

[0079] It should be understood that the above-described methods and apparatus are to be interpreted as including the apparatus for performing the method and the method of using the apparatus. It should be understood that features and / or steps described with respect to one embodiment may sometimes be used in other embodiments, and not all embodiments of the invention have all the features and / or steps shown in all the specific drawings or described with respect to one particular embodiment. Tasks are not necessarily performed in the exact order described.

[0080] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the invention. As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items. As used herein, the singular forms "a," "an," and "the" are intended to include both the plural and singular forms unless the context clearly indicates otherwise. It will be further understood that, when used in this specification, the terms "comprises" and / or "comprising" specify the presence of the stated features, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, steps, operations, elements, components, and / or combinations thereof.

[0081] It should be noted that some of the embodiments described above may include details of structure, behavior, or structure and behavior that may not be essential to the present invention and are described as examples. As is known in the art, the structures and behaviors described herein can be replaced by equivalents that perform the same function, even if the structure or behavior differs. The embodiments described above have been mentioned by way of example, and the invention is not limited to what has been specifically shown and described above. Rather, the scope of the invention includes combinations and sub-combinations of the various features described above, as well as variations and modifications thereof that would occur 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.

Claims

1. A device for implanting a radiotherapy seed source into a tumor, comprising: A delivery tube having a distal end designed to enter the tumor and defining an internal channel; A rotating mechanism configured to rotate the delivery tube within the tumor; and An elongated applicator carrying one or more radiotherapy seed sources, each having a length of at least 1 mm, the elongated applicator passing through the inner channel of the delivery tube. Specifically, when the distal end of the elongated applicator is close to the distal end of the delivery tube, the distal end of the elongated applicator forms an angle with respect to the axis of the delivery tube, such that the seed source ejected from the elongated applicator enters the tumor at an angle relative to the axis of the delivery tube.

2. The apparatus of claim 1, further comprising a core needle within the elongated applicator, the core needle being configured to push one or more radiotherapy seed sources relative to the elongated applicator when the distal end of the elongated applicator is in the tumor, so as to eject the one or more radiotherapy seed sources from the elongated applicator into the tumor.

3. The apparatus of claim 2 further includes a needle handle configured to precisely push the needle relative to the elongated applicator by a distance equal to the length of the seed source at the distal end of the elongated applicator.

4. The apparatus according to claim 3, wherein, The needle handle is configured to push the needle while keeping the elongated applicator stationary.

5. The apparatus according to claim 3, wherein, The needle handle is configured to keep the needle stationary while retracting the elongated applicator.

6. The apparatus according to claim 1, wherein, The distal end of the elongated applicator is configured to eject the seed source from the elongated applicator at an angle of at least 5° relative to the axis of the delivery tube.

7. The apparatus according to claim 6, wherein, The distal end of the elongated applicator is configured to eject the seed source from the elongated applicator at an angle of at least 30° relative to the axis of the delivery tube.

8. The apparatus according to claim 6, wherein, The distal end of the elongated applicator is configured to eject the seed source from the elongated applicator at an angle of at least 45° relative to the axis of the delivery tube.

9. The apparatus according to claim 6, wherein, The distal end of the elongated applicator is configured to eject the seed source from the elongated applicator at an angle of less than 25° relative to the axis of the delivery tube.

10. The apparatus according to claim 6, wherein, The distal end of the elongated applicator is configured to eject the seed source from the elongated applicator at an angle of less than 15° relative to the axis of the delivery tube.

11. The apparatus according to any one of claims 1 to 10, wherein, The elongated applicator includes a nickel-titanium tube.

12. The apparatus according to any one of claims 1 to 10, wherein, The rotating mechanism is configured to stop rotating at a specific radial angle, at which the seed source is implanted.

13. The apparatus according to any one of claims 1 to 10, wherein, The rotating mechanism is configured to rotate the delivery tube within the tumor by a predetermined angle.

14. The apparatus according to any one of claims 1 to 10, wherein, The rotating mechanism includes an indexing rod and a spherical plunger. The indexing rod has a hole at a radial angle, at which the seed source is inserted, and the spherical plunger is installed into the hole.

15. The apparatus according to any one of claims 1 to 10, wherein, The rotating mechanism includes a stepper motor configured to rotate the delivery tube within the tumor to a specific radial angle.

16. The apparatus according to any one of claims 1 to 10, wherein, The inner channel is configured to carry and eject the seed source, and the inner channel has a length of at least 5 millimeters.

17. The apparatus according to any one of claims 1 to 10, wherein, The distal end of the elongated applicator is configured to present an angled bend relative to the axis of the delivery tube when no external force is applied.

18. The apparatus according to any one of claims 1 to 10, wherein, The delivery tube includes a side window facing the distal end of the delivery tube, and wherein the elongated applicator is configured to eject the one or more radiotherapy seed sources through the side window.

19. The apparatus according to claim 18, wherein, The delivery tube comprises two concentric tubes that rotate relative to each other to open and close the side window.

20. The apparatus according to claim 18, wherein, The delivery tube includes a bevel near the side window, the bevel causing the distal end of the elongated applicator to form the angle relative to the axis of the delivery tube.

21. The apparatus according to any one of claims 1 to 10, wherein, The elongated applicator carries at least three seed sources.

22. The apparatus according to claim 21, wherein, The elongated applicator carries at least five seed sources.

23. The apparatus according to any one of claims 1 to 10, wherein, The elongated applicator has a long axis and includes an opening on the long axis at the distal end of the elongated applicator for ejecting the radiotherapy seed source.

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