WO2012067536A1

WO2012067536A1 - High-dosage microsource of radioactive radiation

Info

Publication number: WO2012067536A1
Application number: PCT/RU2011/000088
Authority: WO
Inventors: Андрей Александрович КУДРИН; Александр Альбертович КУЗНЕЦОВ
Original assignee: Kudrin Andrei Alexandrovich; Kuznetsov Alexandr Albertovich
Priority date: 2010-11-15
Filing date: 2011-02-17
Publication date: 2012-05-24

Abstract

The high-dosage microsource of radioactive radiation comprises: a capsule of titanium or vanadium, which is in the form of a hollow tube (3), hermetically sealed at both ends, and which is placed in a housing (1) consisting of stainless steel, with a radioactive material arranged in said capsule; and a flexible line (2) attached to the housing, wherein the radioactive material used is a powder (7) of ytterbium(III) oxide (Yb₂O_з), enriched in the isotope ¹⁶⁸Yb to a content of 35.8±0.3 atomic percent and subjected to neutron radiation to produce the isotope ^l69Yb with an activity of from 0.5 Ci to 15 Ci.

Description

High-dose micro radiation source

The invention relates to medicine, in particular to radiation sources used in brachytherapy, made in the form of containers or capsules of small size, firmly connected to the guide cable.

A known source of radiation for brachytherapy, comprising a capsule-shaped body for placement of radioactive material in it and a guide cable provided with a cylindrical end, on the surface of which circular grooves are made. The capsule is equipped with a smooth-walled cylindrical cavity into which the cylindrical end of the cable with grooves is inserted. After introducing the end of the cable into the cavity, the capsule walls surrounding the cylindrical cavity are crimped, forming an integral connection (patent RU 2357774, IPC A61N5 / 10, published on October 27, 2008). A disadvantage of the known device is the complexity of its manufacture, since titanium is a very fragile material, and the size of the capsules and the portion of the cable with grooves are very small. For example, the outer diameter of the capsule is about 1.06 mm, and the outer diameter of the cavity into which the end of the cable is inserted is about 1.09 mm. In addition, when the end of the cable is crimped by the capsule walls, the walls often break down due to the brittleness of titanium, which entails a decrease in the yield.

Known high-dose micro-source of radioactive radiation (application US 20090246126, IPC A61K51 / 12, published 01.10.2009), which contains as a radioactive material thulium-170, which is coated with a layer of gold, for example, in the form of a foil, and placed in a case in in the form of a capsule made of titanium or stainless steel. A cable is attached to the capsule, which allows the source to be introduced into the human body through a catheter and removed.

A disadvantage of the known device is that the cable is attached either with epoxy glue, which is a relatively weak material rial, or by welding. In this case, dissimilar metals have to be welded, which is difficult from the point of view of technology.

Closest to the claimed device in its technical essence is a known source of radioactive radiation used in brachytherapy (application US 20100099940, IPC A61 M36 / 12, published on 04/22/2010). The source contains a case in the form of a tube made of titanium, in which natural thulium-169 is placed in the form of a wire of small diameter (approximately 0.45-0.65 mm), which is partially covered with gold, which is an X-ray marker, or a dusting, or foil wrap. After thulium is placed in a tube of titanium, the latter is sealed by means of plugs connected to the tube by laser welding. After that, the capsule obtained in this way is placed in a nuclear reactor and thulium-169 is activated as a result of exposure to neutron radiation by converting thulium-169 into thulium-170.

A disadvantage of the known device is that the source casing is made of titanium, which makes it difficult to attach flexible cables to it, allowing the radioactive radiation source to be freely introduced into the patient’s body and removed.

The high-dose micro-source of radioactive radiation claimed as an invention is aimed at providing a flexible connection of the housing with the cable and achieving high doses of radioactive radiation.

This result is achieved by the fact that a high-dose micro-source of radioactive radiation contains a capsule of titanium or vanadium placed in a stainless steel case in the form of a hollow tube sealed at both ends with radioactive material placed in it and a flexible cable attached to the case.

This result is also achieved by the fact that the means of sealing the cavity of the capsule is made in the form of balls of titanium or vanadium, which are connected to the ends of the tube by laser welding.

The specified result is also achieved by the fact that the means of sealing the cavity of the capsule is made in the form of bushings in the form of truncated cones of titanium or vanadium, attached to the ends of the tube by laser welding. The specified result is also achieved by the fact that the means of sealing the cavity of the capsule is made in the form of T-shaped bushings of titanium or vanadium, attached to the ends of the tube by laser welding.

The indicated result is also achieved by the fact that ytterbium oxide powder (Yb ₂ 0 ₃ ) is used as the radioactive material, enriched in the Yb isotope to a content of 35.8 ± 0.3 atomic percent and subjected to neutron radiation to obtain activity from 0 5 Ki to 15 Ki. In this case, the ^l68 Yb isotope is transformed into the ¹⁶⁹ Yb isotope.

The construction of the stainless steel housing makes it relatively easy to attach a flexible cable made of the same material to it. The execution of the capsule with the radioactive material placed in it from titanium is due to the fact that, to activate the source, it is placed in a neutron radiation flux which is so intense that it causes the capsule to be heated to temperatures above the melting temperature of the steel. Therefore, the capsule made of such a refractory material as titanium allows it to be irradiated with a neutron flux with the power required for activation, and its placement inside the stainless steel housing allows solving the problem of attaching a flexible cable to it. In addition, stainless steel is an inert material, which makes it possible to use the proposed radiation source for introduction into the patient's body. In order to exclude the loss of radioactive material placed inside the capsule during its movement into the irradiation zone, when assembling the source, etc., it is advisable to seal the capsule, since the loss of radioactive material also entails economic losses due to its high price and can lead to to radioactive contamination of technological premises. Sealing can be carried out by any of the known methods (for example, flattening the ends of the tube, pressing it into the ends of the bushings, etc.). It is most expedient to carry out sealing using balls or bushings in the form of truncated cones, or T-shaped bushings made of titanium or vanadium, connected to the ends of the tube by laser welding.

The use of ytterbium oxide powder (Yb ₂ (>?), Enriched in the ^{l 68} Yb isotope to a content of 35.8 ± 0.3 atomic percent, as a radioactive material makes it possible to achieve high radiation doses of my source. Furthermore, for the same capsule with the powder of ytterbium oxide (Yb ₂ 0z) is subjected to neutron radiation to obtain ^l69 Yb with an activity of 0.5 to 15 Ki Ki. The flux and fluence of the radiation necessary for this are selected experimentally or by calculation.

The essence of the claimed device is illustrated by an example implementation and figures, which show a diagram of a device with various options for sealing a titanium capsule (see figure 1 - figure 3).

The high-dose micro radiation source contains a housing 1 made of stainless steel to which a flexible cable 2 is attached by any of the known methods (laser welding, argon atmosphere welding, swivel joint). A capsule made of titanium or vanadium is placed inside the housing 1 in the form hollow tube 3, sealed using balls 4 or bushings in the form of truncated cones 5 or T-shaped bushings 6 made of titanium or vanadium, attached to the ends of the tube 3 by laser welding. Powder 7 of ytterbium oxide (Yb ₂ 0 ₃ ) enriched in the ^l68 Yb isotope to a content of 35.8 ± 0.3 atomic percent is placed inside the capsule.

A high-dose micro-source of radioactive radiation is manufactured as follows. Powder is placed in a tube 3 of titanium or vanadium

7 ytterbium oxide (Yb ₂ 0 ₃ ) enriched in the 168 Yb isotope to a content of 35.8 ± 0.3 atomic percent and sealed using 4 balls or truncated cone 5 sleeves or 6 T-shaped sleeves made of titanium or nadium attached to the ends of the tube 3 by laser welding. After that, the capsule is placed under the neutron flux of a nuclear reactor until activity from 0.5 Ci to 15 Ci is obtained. The capsule with the activated radioactive material is placed in a housing 1 made of stainless steel to which a flexible cable 2 is connected and placed in a lead container.

High-dose micro-source of radiation is used as follows. To irradiate the tumor tissue in the patient’s body, the source is introduced into the body by the known methods used in brachytherapy and held in it until the tissue receives the required dose, after which it is removed using a flexible cable 2.

In order to evaluate the radiobiological parameters of the radiation of microsources ^{l 69} Yb, studies were performed on animal tumor carriers with a model tumor of sarcoma M-1 (connective tissue, fast-growing and radioresistant). Used outbred adult rats, males, weighing 160 ± 20 g. The tumor was transplanted subcutaneously into the thigh of the right hind limb. After 12 days, the animals were depilated with cream on the skin of the tumor. This treatment does not injure the skin, and the absence of coat for the next 2-3 weeks allows us to correctly assess the extent of its possible radiation damage, as well as to increase the accuracy of measuring the size of the tumor. The criteria for evaluating the effectiveness of the impact were the dynamics of tumor growth and the degree of damage to the skin above it. The intensity of radiation reactions of the skin was determined visually. In the initial period after the introduction of the source, in the midst phase, the assessment was made every other day, after 2-3 weeks, in the damping phase - 1-2 times a week.

Rats with sarcoma M-1 were placed in a special plastic container of four animals. A ¹⁶⁹ Yb microsource needle was inserted into the center of the tumor to a depth of ~ 4 mm. Based on the calculation data presented above, the duration of irradiation of each tumor was 100 min, which made it possible to irradiate the periphery of the tumor with a dose of at least 30 Gy at a dose rate of ~ 0.3 Gy / min. The radiation efficiency ^l69 Yb was compared with standard gamma radiation of ⁶⁰ Co (Luch-1 installation).

The experimental data were processed using standard statistical analysis methods. The sample mean value (X) and the standard deviation of the mean value (S ^) were calculated.

The results of preliminary studies showed that intratumoral administration of a high-dose source based on ¹⁶⁹ Yb leads to almost complete tumor regression (25 days after irradiation, complete regression of the tumor was observed in 62% of the animals, tumor size was less than 10 in 23% of the animals % of the initial volume) with mild and passing skin reactions.

Thus, a high-dose micro-source of radioactive radiation provides a flexible connection between the body and the cable and allows to achieve high doses of radioactive radiation with a high degree of efficiency of treatment of tumor diseases.

Claims

Claim

1. A high-dose micro-source of radioactive radiation containing a capsule made of titanium or vanadium placed in a stainless steel case (1) in the form of a hollow tube (3) sealed at both ends with a radioactive material placed in it and flexible to be attached to the case cable

(2) at the same time as the radioactive material is a powder (7) Oak sida ytterbium (Yb ₂ 0z) enriched in the isotope ^{68 l} Yb content to 35.8 ± 0.3 atomic percent and subjected to neutron radiation to obtain iso- top ¹⁶⁹ Yb with activity from 0.5 Ci to 15 Ci.

2. A high-dose micro-source of radioactive radiation according to claim 1, characterized in that the means for sealing the cavity of the capsule is made in the form of balls (4) of titanium or vanadium attached to the ends of the tube (3) by laser welding.

3. A high-dose micro-source of radioactive radiation according to claim 1, characterized in that the capsule cavity sealing means is made in the form of bushings in the form of truncated cones (5) of titanium or vanadium attached to the ends of the tube (3) by laser welding.

4. The high-dose micro-source of radioactive radiation according to claim 1, characterized in that the means for sealing the cavity of the capsule is made in the form of T-shaped bushings (6) made of titanium or vanadium, attached to the ends of the tube

(3) laser welding.