RU2430440C1 - Bismuth-212 radionuclide obtaining method - Google Patents

Abstract

FIELD: power industry.

SUBSTANCE: solution containing mixture of radionuclides thorium-228 and thorium-229, as well as daughter decay products of these radionuclides is bubbled with gas, thus extracting from them one of daughter decay products of thorium-228 - gaseous radionuclide radon-220. Gas is supplied through aerosol filter to sorption device where as a result of radioactive decay as per chain ²²⁰Rn→²¹⁶Po→²¹²Pb there accumulated is radionuclide lead-212, which, after attainment of saturation of activity of lead-212, is desorbed. The obtained solution is supplied to column with ion-exchange resin from which the daughter decay product of radionuclide bismuth-212 is washed from time to time. As bubbling gas there used is air and/or nitrogen and/or helium and/or argon and/or krypton and/or xenon. As sorption device there used is hollow volume the dimensions of which provide the residence time of radon-220, which is sufficient for its complete decay to radionuclide lead-212, or trap with activated carbon.

EFFECT: reducing the labour intensity of the process and the content of doping radionuclides.

4 cl

Description

FIELD OF TECHNOLOGY

The invention relates to a technology for producing radionuclides for nuclear medicine and can be used, in particular, for the treatment of cancer.

In the treatment of cancer, α-emitting radionuclides are increasingly used. This is due to the large initial energy (5–8 MeV) and the short range (tens of microns) of α particles in biological tissues and, therefore, the high level of energy release in the localization region of decaying nuclides. Carriers of α-emitting radionuclides (monoclonal antibodies, peptides) with high specificity allow them to be delivered exactly to the tumor node or metastatic focus. Due to the small ranges of α-particles, a selective effect of radiation on pathological objects is possible with a minimum radiation load on surrounding healthy tissues.

The present invention can be used to create generators of α-emitters of thorium-228 / lead-212 ( ²²⁸ Th / ²¹² Pb) and lead-212 / bismuth-212 ( ²¹² Pb / ²¹² Bi), the final elements of the decay chain of which are lead radionuclides - 212 and bismuth-212 can be used as part of medical radiopharmaceuticals.

BACKGROUND OF THE INVENTION

One of the most promising areas in nuclear medicine is radioimmunotherapy using α-emitters. The use of short-lived α-emitting radionuclides for the treatment of cancer is of interest from a radiobiological point of view, since it is the most effective way of lethal damage to tumor cells due to the short range of α-particles in the tissue and high ionizing ability.

A search is currently underway for α-emitters with acceptable nuclear-physical properties. The bismuth-212 radionuclide formed during the decay of the uranium-232 isotope is considered one of the most promising for use in the treatment of cancer.

The half-life of bismuth-212 is 60.6 min; the average energy of α particles is 7.8 MeV. During the decay of bismuth-212, thallium-208 and polonium-212 radionuclides are formed, which lead to the stable lead-208 nuclide. The range of α particles in biological tissue is less than 100 μm, which corresponds to only a few diameters of the cancer cell, and linear energy transfer (LET) reaches ~ 80 keV / μm.

The initial element of the uranium-232 chain is the artificial uranium isotope, the formation of which occurs in a nuclear reactor when natural thorium is irradiated as a result of the following reactions of the interaction of neutrons and gamma rays with thorium-232 nuclide:

²³² Th (n, γ) ²³³ Th → ²³³ Pa (γ, n) ²³² Pa → ²³² U

²³² Th (n, 2n) ²³¹ Th → ²³¹ Pa (n, γ) ²³² Pa → ²³² U

²³² Th (γ, n) ²³¹ Th → ²³¹ Pa (n, γ) ²³² Pa → ²³² U

Depending on the conditions of thorium irradiation in the reactor, the equilibrium concentration of uranium-232 lies in the range of 1000-6000 ppm [V.M. Murogov, M.F. Troyanov, A.N. Shmelev. The use of thorium in nuclear reactors. M .: Energoatomizdat, 1983].

When thorium is irradiated in the reactor simultaneously with uranium-232, the formation of uranium-233 occurs according to the following reaction:

²³² Th (n, γ) → ²³³ Th → ²³³ Pa → ²³³ U

As a result of the α decay of uranium-233, thorium-229 is formed, which, in turn, after a series of decays passes into the radionuclide bismuth-213.

Bismuth-212 is a typical radionuclide generator and is used in radioimmunotherapy, mainly in the form of monoclonal antibodies labeled by it and other molecular carriers. Today, two generator systems are used to produce bismuth-212 - ²²⁸ Th / ²²⁴ Ra and ²²⁴ Ra / ²¹² Bi. In the first of these, radium-224 is separated from thorium-228 due to the anion-exchange separation of these radionuclides from a solution of nitric acid. In a second generator using cation exchange resins and mineral acids, radium-224 is used to isolate bismuth-212 [RWAtcher, AMFriedman, JJHines “An improved generator for the production of ²¹² Pb and ²¹² Bi from ²²⁴ Ra”. International Journal of Radiation Applications and Instrumentation. Part A. Applied Radiation and Isotopes, Volume 39, Issue 4.1988, Pages 283-286].

For the prototype, a method for producing bismuth-212 was described, described in [V. M. Savinov, V. B. Pavlovich, A. A. Kotovsky and others. “Control of technological processes in the development of medical generators ²²⁵ Ac / ²¹³ Bi and ²²⁴ Ra / ²¹² Bi by alpha and gamma spectrometric methods ”// Nuclear Energy, No. 3, 2003, pp. 116-126].

The authors used a solution containing a mixture of thorium-228, thorium-229 radionuclides and decay daughter products of these radionuclides as feedstock for producing bismuth-212 radionuclide. To obtain bismuth-212, the following procedures were performed:

- radionuclides of thorium-229, thorium-228 and the resulting daughter decay products of these radionuclides were kept in a solution of nitric acid to accumulate radionuclide radium-224;

- after exposure, the solution containing the radionuclides of thorium-229, thorium-228, as well as radium-224 and other daughter decay products of thorium-229 and thorium-228, was passed through a column with anion exchange resin;

- radionuclides of thorium-229 and thorium-228 remained in the column with anion exchange resin, and radium-224 and other daughter decay products of thorium-229 and thorium-228 were collected at the outlet of the column;

- the resulting solution containing radium-224 and other daughter decay products of the thorium-229 and thorium-228 radionuclides was evaporated to dryness;

- a dry residue containing radionuclide radium-224 was dissolved in hydrochloric acid;

- an acid solution of radium-224 was passed through a column with cation exchange resin;

- radionuclide radium-224 remained in the column with cation exchanger;

- the column containing the radionuclide radium-224 was washed with a solution of hydrochloric acid;

- at the exit from the cation exchanger column, a solution with bismuth-212 radionuclide was collected.

However, this method of producing bismuth-212 has several disadvantages:

- the multi-stage process for producing bismuth-212 from a mixture of thorium-228 and thorium-229 radionuclides is laborious, carried out by sequential radiochemical separation of radium-224 radionuclide by sorption from the initial solution of thorium-228 and thorium-229 and in the next stage of separation from a solution of radium- 224 radionuclide bismuth-212;

- in the initial solution of thorium-228 and thorium-229 radionuclides during storage, an impurity thallium-208 radionuclide is accumulated, having gamma radiation with an energy of 2.6 MeV, which creates large radiation loads on personnel carrying out the process of producing bismuth-212.

SUMMARY OF THE INVENTION

The objective of the invention is to simplify the process for producing a bismuth-212 radionuclide and to reduce the yield of impurity radionuclides.

To solve the problem in a method for producing a bismuth-212 radionuclide from a solution containing a mixture of thorium-228 radionuclides, thorium-229 and daughter decay products of these radionuclides, followed by the isolation of bismuth-212 using ion exchange resins, a solution containing a mixture of thorium-228 radionuclides and thorium-229, as well as daughter products of the decay of these radionuclides, gas sparging, while removing one of the daughter products of the decay of thorium-228 - gaseous radonuclide radon-220 from the solution, direct gas through an aerosol fil to a sorption device, where, as a result of radioactive decay along the ²²⁰ Rn → ²¹⁶ Po ²¹² Pb chain, accumulate lead-212 radionuclide, which, after the lead-212 activity is saturated, desorb and send the resulting solution to a column with an ion-exchange resin, from which the daughter decay product of radionuclide bismuth-212.

In this case, the solution is sparged with air and / or nitrogen and / or helium and / or argon and / or krypton and / or xenon.

As a sorption device, you can use a hollow volume, the dimensions of which provide a residence time of radon-220, sufficient for its complete decay into lead-212 radionuclide.

An activated carbon trap can be used as a sorption device.

The sorption device (it can be a long tube, or a large vessel, or a trap with a sorbent, for example, activated carbon) should provide a gas flow through it for at least 10 minutes (about ten half-lives of radon-220 - 55.6 s) .

In the proposed method for producing bismuth-212 radionuclide, the presence of gaseous radon-220 radionuclide among daughter products of thorium-228 decay, which, as a result of decay along the chain ²²⁰ Rn → ²¹⁶ Po → ²¹² Pb → ²¹² Bi, leads to the formation of the target radionuclide bismuth-212. The half-life of radon-220 is 55.6 seconds, which makes it possible to remove it from aqueous acid solutions using gas sparging [Radionuclide decay schemes. Energy and radiation intensity. Publication 38 of the ICRP. In two parts. Part two. Book 2. M.: Energoatomizdat, 1987, pp. 204-205].

The inert gas radon is 6.7 times heavier than air, has a low solubility coefficient in water [A.S. Serdyukova, Yu.T. Kapitanov. Radon isotopes and their decay products in nature. M .: Atomizdat, 1975]. Due to its low solubility, radon is easily released from water into air. In thermal waters having a temperature above 30 ° C, the solubility coefficient of radon in water is halved in relation to the so-called "cold" radon waters with temperatures up to 10 ° C. The rapid release of radon into the air is also facilitated by the saturation of thermal radon waters with nitrogen and carbon dioxide. According to some authors, the loss of radon from water with carbon dioxide released from it reaches 36%.

Radon isotopes in extremely rare cases enter chemical compounds. The chemical compounds of radon-220 are not known.

In the presence of floating gas bubbles in the solution, the radon atoms in the process of diffusion in the liquid penetrate into the volume of the bubbles and are carried to the surface of the solution. Transporting radon-220 via technological gas communications, it is delivered to a capture system, where lead-212, which, in turn, disintegrates into bismuth-212, is kept until complete decay.

After removal from the capture system, the bismuth-212 radionuclide is used for its intended purpose for the preparation of medications used in the treatment of cancer.

The proposed method for producing a radionuclide bismuth-212 has advantages compared with the described prototype:

- the bismuth-212 radionuclide obtained in this way does not contain radioactive impurities, since there is only one gaseous radionuclide - radon-220 in the decay chains of thorium-229 and thorium-228;

- eliminates a multi-stage radiochemical redistribution of a solution containing a mixture of thorium-228 and thorium-229 radionuclides and daughter products of the decay of these radionuclides, which simplifies the process of obtaining bismuth-212;

- in the initial solution containing a mixture of thorium-228 radionuclides, thorium-229 and daughter decay products of these radionuclides, the admixture of thallium-208 radionuclide having high-energy gamma radiation is reduced, which reduces the dose burden on personnel.

MODE FOR CARRYING OUT THE INVENTION

As a feedstock for producing the bismuth-212 radionuclide, a solution containing a mixture of thorium-228, thorium-229 radionuclides and decay daughter products of these radionuclides is used.

To obtain bismuth-212, a mixture of thorium-229, thorium-228 radionuclides and the resulting daughter decay products of these radionuclides is kept in an acidic HNO ₃ solution placed in a 50 ml bubbler flask. The total volume of the solution is 10 ml. Air is supplied to a bubbler flask through a tube immersed in an acid solution using a peristaltic pump at a flow rate of ~ 50 ml / min. As the pumped gas, any of the gases mentioned in the formula or mixtures thereof can be used. Air was selected as the most affordable gas.

By gas communication, which is a fluoroplastic tube 0.3 m long from a bubbler bulb, an air stream containing radon-220 atoms is fed to an aerosol filter to separate the dispersed fraction of the initial solution. After passing through the filter, the air flow enters the sorption volume, which is a fluoroplastic tube with a diameter of 8 mm and a length of more than one meter. The residence time of the gas stream in the tube of the specified length is sufficient for the complete decay of radon-220 and the sedimentation of its daughter radionuclide lead-212 on the wall of the tube. The purified air in a closed circuit again enters the bubbler flask with a solution of radionuclides thorium-229 and thorium-228.

The duration of gas pumping along the circuit is 20 hours, which is more than 60% of the time required for the lead-212 radionuclide to become saturated. After pumping is complete, the tube is disconnected from the unit and lead-212 is desorbed from its internal surface.

The desorption of lead-212 is carried out sequentially by two solutions: hot water with a volume of 50 ml and 6M HCl with a volume of 50 ml (thorium-228 generator / lead-212).

From the obtained hydrochloric acid solution, lead-212 and bismuth-212 radionuclides are sorbed on Dowex-50 cation exchanger and, as the amount of accumulation and the need for the weak hydrochloric acid solution, the necessary amount of bismuth-212 is desorbed (lead-212 / bismuth-212 generator).

All solutions, including the solution in the bubbler flask, are subjected to spectrometric analysis to determine the radionuclide composition and information on the material balance.

The proposed method for producing bismuth-212 allows, in comparison with the method selected for the prototype, to reduce the complexity of the process, to reduce the content of impurity radionuclides.

Claims (4)

1. A method of producing a bismuth-212 radionuclide from a solution containing a mixture of thorium-228 radionuclides, thorium-229 and daughter decay products of these radionuclides, followed by isolation of bismuth-212 using ion-exchange resins, characterized in that the solution containing a mixture of thorium-radionuclides 228 and thorium-229, as well as daughter decay products of these radionuclides, are sparged with gas, while removing one of the daughter decay products of thorium-228 - gaseous radonuclide radon-220 from the solution, direct gas through an aerosol filter to a sorption device o, where the radioactive decay chain ²²⁰ Rn → ²¹⁶ Po → ²¹² Pb accumulate radionuclide lead-212, which is after 212 lead activity saturates desorbed and the resulting solution was fed to a column of ion exchange resin, which are periodically rinsed daughter decay product radionuclide bismuth-212. 2. The method according to claim 1, characterized in that the solution is sparged with air and / or nitrogen and / or helium and / or argon and / or krypton and / or xenon. 3. The method according to claim 1, characterized in that as a sorption device using a hollow volume, the dimensions of which provide a residence time of radon-220, sufficient for its complete decay into radionuclide lead-212. 4. The method according to claim 1, characterized in that an activated carbon trap is used as a sorption device.