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 (T1/2=60 min),213Bi (T1/2=45,6 min),225AU (T1/2=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 T1/2=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)230230U (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)230230U 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)230230U 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.



 

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