RU162364U1 - LOW DOSE ITTERBIUM SOURCE - Google Patents

Abstract

1. A source for low-dose brachytherapy, made in the form of a thin-walled hermetically sealed titanium capsule containing ceramic cores from a mixture of a basic compound that weakly absorbs gamma radiation from the ytterbium Yb-169 radioactive isotope and ytterbium oxide impurities with a biased isotopic composition, highly enriched in ytterbium isotope -168 and Yb-174 depleted in ytterbium isotope, while the concentration of ytterbium Yb-168 in the mixture exceeds the concentration of ytterbium Yb-174 by at least three times. 2. A source according to claim 1, characterized in that the main compound is made in the form of graphite, oxides or hydroxides of light elements. A source according to claim 2, characterized in that aluminum or silicon are used as hydroxides of light elements. A source according to claim 1, characterized in that the ceramic cores are obtained by pressing followed by annealing. The source according to claim 1, characterized in that the highly enriched ytterbium isotope Yb-168, at least 75%, is used.

Description

The technical field to which the utility model relates.

The utility model relates to radioactive sources used in brachytherapy of cancer. Brachytherapy is a cancer treatment method in which radiation sources are placed in the body directly in the tumor area. With high-dose brachytherapy, a radioactive source is introduced into the focal area using catheters with the possibility of remote movement through the catheters in accordance with the irradiation plan.

Brachytherapy is a promising high-tech area in the radiotherapy of malignant tumors and is based on the introduction of sealed radioactive sources directly into the tumor or into nearby tissues. This operation is carried out under visual control using ultrasound or fluoroscopy and allows for radical treatment even in the case of complex localization of tumors, when conventional remote therapy or surgery is not indicated due to the proximity of critical organs. According to the dose rate and properties of the sources used, brachytherapy is divided into low-dose brachytherapy (NDB) and high-dose brachytherapy (VDB), the foreign abbreviation is LDR and HDR, respectively. NDB has been widely used, since with a low dose rate of ~ 0.5 Gy / h, an optimal therapeutic effect is achieved.

The clinical advantages of NDB brachytherapy are due to the fact that during this treatment, due to the relatively low-dose dosage, reparation processes in healthy tissues surrounding the tumor have time. Sources containing isotopes I-125, Pd-103, etc. are widely used for conducting NDB. These sources have radiation with a short range in the tissues of the patient's body (energy 20-30 KeV). Therefore, for example, up to 200 sources are introduced into the tumor of the prostate gland, which remain there forever.

With the help of BPD, impressive advances have been achieved in the treatment of prostate cancer (PCa). In patients with the first stage of prostate cancer, the average 5-year survival after NDB is about 90%.

State of the art

Sources for brachytherapy are generally a sealed capsule made of various materials (for example, inorganic), inside which a radiation source in the form of a core of radioactive material is placed. These are the so-called closed radionuclide sources (RF patents 2277953, op. 20.06.06, 2251437, op 10.05.05. 2343935, 01.20.09, 101367, op. 20.01.2011, US patent 7530941, op. 12.05.09).

Also known from the prior art is a source based on ytterbium-169. For the first time, ytterbium-169 sources were used in low-dose therapy in the form of low activity seeds (needles) in 1993, US Patent WO 2005/023367 A3, X-Ray And Gamma Ray Emitting Temporary High Dose Rate Brachyterapy Source.

The prior art source for brachytherapy, described in the patent of the Russian Federation for utility model, No. 101367 op. 01/20/2011. The source is a sealed capsule, which can be made of various inorganic materials, aluminum, titanium, etc., in which there is a core containing ytterbium with a concentration of ytterbium-168 isotope in the range of 15-30 at. % The density of the partially porous core material lies in the range of 5-8.5 g / cm ³ . After irradiation of the capsule in the channel of an atomic reactor, the ytterbium-169 radionuclide is formed in it, the radiation energy of which does not exceed 310 keV, and the source activity can reach 30 Ci. A continuous sealing coating is applied to the outer surface of the capsule, which can be made of metals or metal oxides or nitrides with a thickness of 0.5-5.0 μm. The coating may also be a nickel-phosphorus coating. The sealed capsule with the core is then placed in a stainless steel container with a leash and, as such, is used in high-dose brachytherapy devices.

As a prototype of the proposed ytterbium source is considered, for example, iodine (iodine 125) isocord microsource Eckert-Ziegler. The description is on the Eckert-Ziegler website, as well as, for example). Isocord micro sources are capsules interspersed at regular intervals with absorbable spacers inside the absorbable suture. Spacers are used to separate sources from each other and prevent their displacement inside the thread. The thread and spacers are made of surgical suture material. The capsule is a 4.5 × 0.8 mm medical titanium cylinder sealed from both ends with a laser, inside the cylinder there is a gold wire - an X-ray marker and a 1-125 radionuclide in the form of silver iodide, which is located in porous alumina ceramics. Microsources are supplied sterile in a protective cassette providing almost complete (> 99%) absorption of low-energy characteristic and gamma radiation. The number of sources in the cartridge is formed on the basis of customer requirements and usually does not exceed 75 pieces. The material of the thread and spacers after implantation are absorbed in the tissues, the capsules remain at the site of implantation.

The disadvantage of the prototype source of NDB based on iodine125 is the low radiation energy and, accordingly, the low range of radiation in the tissues. This leads to the need to introduce into the field of interest a significant number of sources for confident overlapping of the tumor zone. To illustrate, Table 1 shows the values of the half-attenuation layers of some isotope radiation. In addition, there is another significant drawback of sources based on iodine-125. The rate of dose delivery to the tumor, determined by the decay time of the isotope, is often insufficient to control tumor growth. In clinical practice, this leads to the fact that for tumors of a sufficiently large volume of NDB with iodine sources is not recommended.

Utility Model Essence

The problem solved by the claimed utility model is to expand the possibilities of using low-dose brachytherapy for large-volume fast-growing tumors and to reduce traumatic tissue damage when sources are introduced into the tumor zone.

The technical result of the claimed utility model is to increase the range of gamma radiation and to increase the dose rate.

The technical result of the claimed utility model is achieved due to the fact that the source for low-dose brachytherapy, made in the form of a thin-walled hermetically sealed titanium capsule containing ceramic cores from a mixture of the main compound, weakly absorbing the gamma radiation of the ytterbium Yb-169 radioactive isotope, and ytterbium oxide impurities with displaced isotopic composition, highly enriched in ytterbium isotope Yb-168 and depleted isotope of ytterbium Yb-174, while the concentration of ytterbium in the mixture of Yb-168 exceeds the concentration and terbium Yb-174 is not less than three times.

In the particular case of the implementation of the claimed utility model, the main compound is made in the form of graphite, oxides or hydroxides of light elements.

In the particular case of the implementation of the claimed utility model, aluminum or silicon were used as hydroxides of light elements.

In the particular case of the implementation of the claimed utility model, ceramic cores were obtained by pressing followed by annealing.

In the particular case of the implementation of the claimed utility model, the highly enriched ytterbium isotope Yb-168, not less than 75%, is used.

Utility Model Disclosure

To overcome the difficulties of the closest analogue and achieve the claimed technical result, it is proposed to use a promising source based on ytterbium Yb-169 for low-dose brachytherapy (NDB).

The advantages of using the claimed source is due, firstly, to the fact that, with a relatively soft energy spectrum, the path of radiation of ytterbium Yb-169 is about 2 times greater than for iodine-125. Secondly, they provide a higher dose rate (the half-life for ytterbium Yb-169 is approximately half that for iodine-125).

Nuclear-physical properties of ytterbium Yb-169:

- the center of the ytterbium emission spectrum of Yb-169 is located in the region of 90 Kev, high specific activity (21 kCi / g), thermal neutron activation cross sections -2400 barn, half-life is 32 days.

Clinical benefits:

- ytterbium sources due to a more intensive dose adjustment compared to iodine sources can remove the restriction on the size of the focus in the treatment of prostate cancer and reduce the number of implantable sources due to the greater mileage of radiation in tissues compared to iodine-125.

From table 1 it can be seen that the mileage of ytterbium Yb-169 radiation in the tissue is about 2 times greater than for iodine I-125, therefore, to confidently cover a given area, the number of ytterbium sources can be significantly less than the number of iodine sources (approximately in the ratio (4.125 / 2) ³ = 8.8). Considering the fact that the absorbed dose in the tissue for ytterbium radiation is approximately 3 times greater than for the radiation of iodine I-125 source of the same activity, approximately 20 times less ytterbium sources are needed to create the same focal dose. Of course, this is a simplified approach, since in a real situation for a more conformal exposure of the region of γ interest, it may be necessary to use two (or more) types of sources with different energies.

It should be noted that the isotopic composition of the initial (starting) material strongly affects the characteristics of the ytterbium source for low-dose brachytherapy. It is known that when the starting material is irradiated with thermal neutrons in the reactor (for the isotopic composition see Table 2), the following isotopes are activated

The contribution of gamma radiation from the activation of ytterbium Yb-176 can be neglected. The average radiation energy for the ytterbium spectrum is Yb-169 ~ 93 KeV, and for the ytterbium isotope Yb-175 - 396 KeV. The half-life of the ytterbium isotope Yb-175 is 4.185 days.

Here are some of our data on the results of irradiation of ytterbium sources at the RIAR at an irradiation time of 19.57 eff. days (19.57 × 24 × 3600 sec = 1.69 * 10 ⁶ sec) and with a thermal neutron flux of 4 * 10 ¹⁴ n / cm ² sec. The neutron fluence was f = 6.8 * 10 ²⁰ n / cm ² . The achieved activity values for ytterbium were Yb-169 = 5.3 Ci, while for ytterbium Yb-175 = 1.2 Ci, that is, the contribution of the undesirable high-energy component to the full emission spectrum of ytterbium Yb-169 is more than 20%, which is unacceptable from a clinical point of view.

Sources for NDB must meet the following requirements: -Dimensions: diameter about 0.8 mm, length 4-5 mm,

- ytterbium oxide core mass ~ 3.5 mg

- contribution to the absorbed dose of the line with an energy of 396 KeV (YM75) - not more than 10%

- activity of about 1 mCi,

- container material - titanium.

The experimental data available in the literature and our data show that the use of sources of non-enriched ytterbium (natural) composition with ytterbium content of Yb-168 C = 0.14% for the manufacture of LDPs is unpromising due to the significant contribution of the high-energy component 396 keV of the ytterbium isotope Yb-175 .

The main difficulty in this case is due to the presence in the isotopic composition of a significant content of the ytterbium isotope Yb-174, the activation of which leads to the appearance of highly active ytterbium Yb-175, which creates gamma radiation with an energy of 396 KeV. The activity of this isotope under the studied irradiation conditions is approximately ~ 25% of the activity of ytterbium Yb-169 at close concentrations of ytterbium Yb-169 and ytterbium Yb-174 (see table). The contribution of the radiation from the interfering ytterbium isotope Yb-174 can be reduced by lowering its concentration in the isotopic composition. In order to reduce the contribution of ytterbium ytterbium Yb-175 radiation to the total absorbed dose by a factor of ~ 3 (not more than 10%, i.e., a ratio of 25/10 = 2.5), it is necessary that the concentration of ytterbium Yb-168 in the starting material exceed the concentration ytterbium - 174 no less than three times.

An attempt to reduce the contribution to the total radiation dose of the 396 KeV line due to exposure of the NDB source for 3 half-lives (~ 12 days) of ytterbium-175 leads to a decrease in the activity of ytterbium Yb-169 by ~ 30%, which is undesirable. Therefore, to create a source based on ytterbium Yb-169, it is necessary to use the highly enriched ytterbium isotope Yb-168, which is in the form of an impurity in a weakly absorbing matrix. If we focus on sources of commercially available reactors with a normal thermal neutron flux density P = 1.0 * 10 ¹³ n / cm ² sec, then to achieve the desired activity of 1 mCi in a given geometric volume, it is necessary to use ytterbium with Yb-168 enrichment of at least one%. Therefore, to create such micro sources, the relatively low enriched ytterbium isotope Yb-168 can be used. In principle, such an isotope could be obtained by small enrichment in the process of isotope separation. However, it is not possible to achieve a decrease in the content of the interfering isotope of ytterbium Yb-174. Therefore, our solution proposes a different way to solve this problem, namely the use of dilution of previously highly enriched ytterbium Yb-168. In the isotopic composition of highly enriched ytterbium Yb-168 (75 ... 85%), the concentration of the interfering ytterbium isotope Yb-174 is less than 5%.

Ytterbium oxide with a natural content of isotopes cannot be used as a diluent, since this will lead to an increase in the concentration of ytterbium Yb-174 to a natural content of ~ 32.6%.

Therefore, it is necessary to use a diluent that meets the following requirements: 1) the absence of ytterbium Yb-174, 2) the absence (or small contribution) of own gamma radiation after irradiation with a thermal neutron flux in the reactor, 3) a sufficiently small absorption of gamma radiation in the range of 50-220 KeV . These requirements are met, for example, by the initial highly enriched ytterbium Yb-168 (75 ... 85%) isotope and highly pure compounds Al ₂ O ₃ and SiO ₂ . Such requirements for the enrichment of ytterbium Yb-168 are necessary to ensure a low (less than 5%) concentration of the interfering isotope of ytterbium Yb-174. For a ceramic core weighing ~ 3.5 mg, compressed from a mixture consisting mainly of alumina with the addition of, for example, 0.2% (by weight) highly enriched (ytterbium Yb-168 - 85%, ytterbium Yb-174 - 5% ) ytterbium oxide

Al ₂ O ₃ + Yb ₂ O ₃ (0.2%)

when irradiated with a thermal neutron flux, P = 1.0 * 10 ¹³ n / cm ² sec (fluence = 1.7 * 10 ¹⁹ n / cm ²⁾ , the estimates given in Table 3 can be obtained.

In the last column of the table. Figure 3 shows the cost of a highly enriched starting material (mass - 0.007 mg) required for the manufacture of this source. The largest contribution to the cost of the source's NDB can be made by the manufacturing costs. In particular, at present, the cost of manufacturing the capsule, laser sealing and leak testing is approximately 1,500 rubles. With the transition to mass production, these costs will significantly decrease.

Here is an example of the implementation of the manufacture of ceramic sources for NDB according to the above methodology.

Since the powder of aluminum oxide Al ₂ O _{3 is} poorly pressed, instead of it was used the powder of aluminum hydroxide Al (OH) ₃ , which is pressed much better. In this case, after pressing by heating the obtained sample at a temperature above 250 ° C, the hydroxide decomposes by the reaction 2Al (OH) ₃ → Al ₂ O ₃ + 3H ₂ O, followed by drying of the water.

1. To prepare a mixture of Yb ₂ O ₃ with Al ₂ O _{3 of the} desired concentration of ~ 0.1%), based on the above reaction, weighed samples were taken: 3 mg of Yb ₂ O ₃ and 3088 mg of Al (OH) ₃ .

2. The powder of laser-enriched (table 2) ytterbium oxide (3 mg) was placed in a plastic container, 10 mg of aluminum hydroxide was added thereto. The container was covered and the powders mixed for 5 minutes. by shaking the container. Then the mixture was poured into an agate mortar, acetone was added so that its surface completely covered the powder, and the mixture was carefully ground for 1-2 minutes. until acetone is completely evaporated.

3. The resulting mixture was placed in a plastic container, 50 mg of aluminum hydroxide was added thereto, the container was closed with a lid and the powders were mixed for 5 minutes. by shaking the container. Then the mixture was poured into an agate mortar, acetone was added so that its surface completely covered the powder, and the mixture was carefully ground for 2-3 minutes. until acetone is completely evaporated.

4. The resulting mixture was placed in a plastic container, 300 mg of aluminum hydroxide was added thereto, the container was closed with a lid and the powders were mixed for 5 minutes. by shaking the container. Then the mixture was poured into an agate mortar, acetone was added so that its surface completely covered the powder, and the mixture was carefully ground for 3-4 minutes. until acetone is completely evaporated.

5. The resulting mixture was placed in a plastic container, 1000 mg of aluminum hydroxide was added thereto, the container was closed with a lid and the powders were mixed for 5 minutes. by shaking the container. Then the mixture was poured into an agate mortar, acetone was added so that its surface completely covered the powder, and the mixture was carefully ground for 4-5 minutes. until acetone is completely evaporated.

6. The resulting mixture was placed in a plastic container, the remaining 1728 mg of aluminum hydroxide was added thereto, the container was closed with a lid and the powders were mixed for 5 minutes. by shaking the container. Then the mixture was poured into an agate mortar, acetone was added so that its surface completely covered the powder, and the mixture was carefully ground for 5-6 minutes. until acetone is completely evaporated.

7. 6 samples of the resulting mixture were taken for spectral analysis. The analysis showed that the ratio of the intensity of the ytterbium and aluminum lines for all six samples is the same up to an error of measurements. This indicates a high degree of homogeneity of the resulting mixture.

8. Samples were pressed from the resulting mixture, which were then placed in a muffle furnace for 1 hour at a temperature of 1200 ° C to convert aluminum hydroxide to aluminum oxide, remove the resulting water and sinter the material.

Claims (5)

1. A source for low-dose brachytherapy, made in the form of a thin-walled hermetically sealed titanium capsule containing ceramic cores from a mixture of a basic compound that weakly absorbs gamma radiation from the ytterbium Yb-169 radioactive isotope and ytterbium oxide impurities with a biased isotopic composition, highly enriched in ytterbium isotope -168 and ytterbium-depleted Yb-174, while the concentration of ytterbium Yb-168 in the mixture exceeds the concentration of ytterbium Yb-174 by at least three times. 2. A source according to claim 1, characterized in that the main compound is made in the form of graphite, oxides or hydroxides of light elements. 3. A source according to claim 2, characterized in that aluminum or silicon are used as hydroxides of the light elements. 4. A source according to claim 1, characterized in that the ceramic cores are obtained by pressing followed by annealing. 5. The source according to claim 1, characterized in that the highly enriched ytterbium isotope Yb-168 is used, at least 75%.