Way of reception of uranium-230 radionuclide for therapy of oncologic diseases

FIELD: medicine.

SUBSTANCE: invention concerns radionuclide reception ²³⁰U for therapy of oncologic diseases. The invention allows simplifying process of manufacture of a radio drug on the basis of short-living α-nuclides due to a natural radionuclide ²³⁰Th. The way includes irradiation of the target containing a natural isotope of thorium - ²³⁰Th in a proton beam of a cyclotron. A target radioactive isotope ²³⁰Th is accumulated in a target in the course of threshold nuclear reaction ²³⁰Th (p, n) ²³⁰Pa→²³⁰U. As a target material bonds of ²³⁰ThF₄ or ²³⁰ThO₂ or metal ²³⁰Th are used. The irradiated target is taken from the accelerator, held and exposed to radiochemical clearing for radioactive isotope reception ²³⁰U of standard quality. The chain of natural disintegration of an isotope ²³⁰U leads to an output of the α-particles used in a nuclear medicine for therapy of oncologic diseases.

EFFECT: simplification of process of manufacture of a radio drug on the basis of short-living α-nuclides due to a natural radionuclide ²³⁰Th.

2 cl, 1 dwg

The invention relates to a technology for production of radionuclides for nuclear medicine on the accelerator.

In the diagnosis and treatment of oncological diseases becoming more widely used are α-emitting radionuclides. This is due, primarily, nuclear-physical properties of these nuclides large initial energy of α-particles (5-8 MeV), short run of these particles in biological tissues (tens of microns) and a high level of energy in the field of localization decaying nuclides. The native α-emitting radionuclides (monoclonal antibodies, peptides with high specificity can deliver them right into the tumor site or metastatic lesion. Possible selective irradiation of pathological objects with minimal radiation exposure to surrounding benign tissue.

The present invention can be used to obtain α-emitter uranium-230 (²³⁰U)used for radioimmunotherapy of cancer.

PRIOR art

Recently for the treatment of malignant neoplasms intensively developed radiopharmaceuticals, basic elements of which are α-emitting radionuclides, fixed in the design of chelating (mounting) component" + "address component is" (antibodies or fragments thereof, specific to antigens of tumor cells, and the ligands of receptors located on their surface).

This molecular design (bioconjugate with radionuclide) is injected to the patient. As these molecular structures have a specific ability to bind only to the surface of a cancer cell, then the process directed delivery of α-emitting radionuclide to a malignant cell. Irradiation of malignant cells α-particles leads to their destruction and death.

α-Emitters are best suited to treat micrometastases and showed high efficiency in the treatment of such a type of blood cancer, as myeloid leukemia. It was also demonstrated their potential application in the treatment of other malignant tumors of melanoma, breast cancer, prostate and lung.

After the death of tumor cells radiopharmaceutical drug products must be safe for normal cells, do not induce side effects (in particular, immunological reactions and actively excreted from the body.

Among the promising α-emitters consider radionuclides²¹²Bi (T_1/2=60 min),²¹³Bi (T_1/2=45,6 min),²²⁵AU (T_1/2=10,0 d) (Wahlbin and other Radionuclides for radiotherapy. Radiochemistry, 1997, t, No. 6, str-490).

When radioimmunotherapy, especially in the initial stevepavlina malignant cells, effectively using radionuclide²³⁰U - α-emitter with a high linear energy transfer (let (~80 Kev/µm) and short run of particles in biological tissue (50-90 μm) with a half-life of T_1/2=20.8 days. Together with daughter decay products in total, 5 is emitted α-particles with a total energy of 33.5 MeV.

A prototype of the selected method of obtaining²³⁰U on the accelerator of protons due to the reaction²³²Th(p,3n)²³⁰→²³⁰U (A.Morgenstem, C.Apoistolidis, F.Bruchertseifer et al. Cross-sections of the 232Th (p,3n)230Pa for production of 230U for targeted alpha therapy". Applied Radiation and Isotopes, vol.66, 2008, Articles in press, the application of the same authors WO No. 2006003123, op).

However, this method has significant drawbacks:

- cross section for the reaction²³²Th(p,3n) has a high threshold, therefore, the implementation process requires the use of high-energy proton accelerator;

- when exposed²³²Th protons with initial energy of 30-40 MeV in the target occurs mainly fission, which produce large quantities of fission products, significantly complicating radiochemical stage of preparation of a medicinal product on the basis of the²³⁰U.

DISCLOSURE of INVENTIONS

The task of the invention is to simplify the process of obtaining²³⁰U, the lower output of the impurity radionuclides and use for the production of the target radionuclide is isoenergetically accelerators of protons with the energy of 10-15 MeV, widely available, easy to use and found a mass application for the production of radionuclides for medical purposes directly in hospitals.

The problem is solved by the fact that in the method of producing a radionuclide²³⁰U for cancer treatment, including radiation on the accelerator of charged particles to the target, as the target material using natural isotope of thorium -²³⁰Th, the target is irradiated with the proton beam accelerator, and the resulting threshold nuclear reactions²³⁰Th(p,n)²³⁰Pa→²³⁰U accumulate in target targeted radionuclides²³⁰U.

As the target material can be used compounds of thorium - 230²³⁰ThF₄or²³⁰ThO₂or metal²³⁰Th.

The drawing shows the decay scheme of the radionuclide²³⁰U.

In the proposed method of production of a radionuclide²³⁰U used the existence of natural radionuclide²³⁰Th - product of the natural decay of²³⁸U. it is Known that radioactive decay of²³⁸U in the chain of child products in addition to isotope²³⁴U are formed long-lived α-emitters: isotope²³⁰Th, and isotope²²⁶Ra with half-lives respectively 7,5·10⁴and 1.59·10³years. The content of these isotopes in natural uranium is estimated following qi is Rami: radium-226 - 352 mg/t of uranium and thorium-230 and 17.9 g/t of uranium. When uranium ore processing described above, α-radioactive isotopes emit as a by-product in the production of uranium (Webscience, Benadryl. The technology of uranium. - M.: gosatomizdat, 1961).

The enriched uranium hexafluoride UF₆thorium-230 is separated and remains in the "stubs" when fluoridation (Matveev L.V. and other Problem of accumulation of²³²U and²³⁶Pu in a nuclear reactor. Nuclear technology abroad. 1980, No. 4, p.10-17). However, the main source of²³⁰Th, available for use at present, are waste dump UF₆in the separation plant during long-term storage is its accumulation (Smirnov J.V. and other Treatment, destruction and disposal of wastes of mining and metallurgical production. Nuclear technology abroad. 1981, No. 3, p.15-20).

The irradiation of targets containing thorium-230, on the proton accelerator in the nuclear reactions²³⁰Th(p,n)²³⁰Pa→²³⁰U accumulate the target radionuclide²³⁰U.

The resulting nuclear reactions²³⁰Th(p,n) radionuclide uranium-230 separated from irradiated targets traditional radiochemical method, widely used in the nuclear industry. Separation of radionuclides²³⁰Th,²³⁰Pa and²³⁰U done with the use of ion exchange resins.

Received radio is uclid uranium-230 used for making medicines, used in the treatment of cancer.

The proposed method of obtaining α-emitting radionuclide uranium-230 has significant advantages in comparison with the described prototype:

- targeted radionuclide²³⁰U get in the reaction (p,n), with a low energy threshold and allowing the use of accelerators with the energy of the protons 10-15 MeV, which is widely used for the production of radionuclides for medical purposes;

- due to the low initial proton energy of impurity related radionuclides minimized;

- targeted radionuclide²³⁰U get, using as starting material a by-product in the processing of uranium ore -²³⁰Th.

An EXAMPLE of carrying out the INVENTION

The target containing²³⁰Th, place on the proton accelerator-cyclotron-type Cyclone 18/9. During irradiation of the target in the threshold of nuclear reactions²³⁰Th(p,n)²³⁰→²³⁰U accumulate radionuclide²³⁰U, which is the target radionuclide and used to prepare therapeutic drug.

After irradiation target with the accumulated therein radionuclide²³⁰U is extracted from the accelerator and kept in a month. At the time that the target is in the β-decay of the intermediate radionuclide²³⁰P is accumulated ²³⁰U. during radiochemical processing of the target material in strongly acidic solutions starting radionuclide²³⁰Th adsorb to the anion exchange resin. When the sorption of radionuclides²³⁰RA and²³⁰U is separated in the form of a solution of the raffinate.

The raffinate, containing a large number of²³⁰RA and²³⁰U, are used for accumulation and excretion²³⁰U.

To obtain²³⁰U high radionuclide purity consistently spend two cycles of sorption separation of the raffinate using ion-exchange columns with different geometries.

The proposed method of obtaining²³⁰U allows for a comparison with the method chosen for the prototype, to reduce the complexity of the process to use as source material by-product uranium production²³⁰Th, to reduce the content of impurity radionuclides.

1. A method of producing a radionuclide uranium-230 for cancer treatment, including the irradiation target with proton beam accelerator, characterized in that as the target material take natural isotope of thorium, thorium-230, the target is placed on the proton beam accelerator, irradiated with protons, and in the process threshold nuclear reactions²³⁰Th(p,n)²³⁰→²³⁰U store it trust radioisotope uranium-230.

2. The method according to claim 1, characterized in that as the target material take is soedineniya ²³⁰ThF₄or²³⁰ThO₂or metal²³⁰Th.