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Bi-213 Generator for Radiotherapy

#2695


Development of Ac-225/Bi-213 Generator and Radiopharmaceuticals on the Basis of Bi-213 Eluate for Radiotherapy

Tech Area / Field

  • MED-RAD/Radiomedicine/Medicine
  • CHE-RAD/Photo and Radiation Chemistry/Chemistry
  • FIR-EXP/Experiments/Fission Reactors
  • FIR-ISO/Isotopes/Fission Reactors
  • FIR-NOT/Nuclear and Other Technical Data/Fission Reactors

Status
3 Approved without Funding

Registration date
05.02.2003

Leading Institute
FEI (IPPE), Russia, Kaluga reg., Obninsk

Supporting institutes

  • Medical Radiological Scientific Center, Russia, Kaluga reg., Obninsk

Collaborators

  • Isonics Corporation, USA, NJ, Closter\nBio-Nucleonics, Inc., USA, FL, Miami

Project summary

The goal of the proposed inter-departmental project is performance of a complex physical and chemical, radiochemical, and biological tests and trials with resolving all problems associated with the raw material recovery, development of Ac-225/Bi-213 medical generator and radiopharmaceuticals on this base, specific immunoglobulins, carrying out biological trials for evaluation of pharmaceutical effectiveness.

The following tasks have to be accomplished during the project implementation:


- establishment of regular production of the parent radionuclide Th-229(228) used for loading into the “raw” (starting) generator of Th-229(228)/Ac-225,
- development of experimental medical generator of Ac-225/Bi-213 for the operation directly in hospitals,
- development of an express-analysis method of the medical generator eluate composition for Bi-213 concentration and for purity in Ac-225 in order to apply it directly in hospitals,
- development of specific immunoglobulin - metallothionein conjugation technology,
- development of a production technology of a cold kit for the Ac–225/Bi-213 generator on the basis of the immunoglobulin-metallothionein conjugate,
- carrying out of preliminary biological trials of the Bi-213 eluate and the pharmaceutical labeled with Bi-213.

The complex of the activities described in this project was necessitated due to the fact that a significant growth of malignant diseases has been registered in developed countries in recent decade, the demand for therapeutic radiopharmaceuticals (RPhC) being far from completely met in terms of quantity or nomenclature. On the other hand, in spite of wide use of beta-emitting radionuclides for oncologic disease treatment, there are significant advantages with alpha-emitters. The said advantages of alpha-emitting radionuclides include a high therapeutic effect due to the intracellular irradiation of a malignant tumor by a-particles. When 1 to 4 a-particles pass through the mammal cell nucleus, the cell is destroyed nearly completely due to the high linear energy transfer (LET), whereas for a similar effect with b-emitters, over 1,000 b-particles are required. The short path of a-particles in tissues provides for the low absorbed dose in healthy organs and tissues.

Bi-213 (T1/2 = 45.6 min) is the most perspective among a-emitting radionuclides, besides, it is a generator-produced radionuclide (Ac-225/Bi-213). In order to use Bi-213 radionuclide effectively in hospitals it is necessary to develop cold kits for the Ac-225/Bi-213 generator, and its composition must make it possible to obtain a labeled pharmaceutical with high radiochemical yield within a short period of time, analogous to the cold kits for Tc-99m and Re-188 generators.

During the Project implementation we plan to perform the complex physical and chemical, radiochemical, and biological tests and trials with resolving all problems associated with the raw material recovery, development of Ac-225/Bi-213 medical generator and radiopharmaceuticals on this base, specific immunoglobulins, carrying out biological trials for evaluation of pharmaceutical effectiveness.

As a result of the Project implementation within two years a basis for the whole production cycle of the alpha-radiopharmaceuticals based on Bi-213 eluate will be developed. This cycle includes the production of the raw material for the Ac-225/Bi-213 medical generator, the generator itself, the procedure of its operation in a hospital, the production technology of pharmaceuticals on the basis of the generator eluate and the model conjugate immunoglobulin-metallothionein.

Afterwards this technology will make it possible to develop radiopharmaceuticals on the basis of monoclonal antibodies that are specific to certain tumors.


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