In the last decade, the production and usage of radionuclides has had widespread success in medical applications. The main goal of this project is the development of a method of obtaining the isotope 67Ga with 18 MeV proton beam and launching its trial production for delivery to the clinics in Armenia and countries in the region.
A medical radioisotope can be classified as a diagnostic or a therapeutic radionuclide depending on its decaying properties. In general, depending on the type of radiation, the diagnostic isotopes are classified into two groups: ?+-emitters (13N, 15O, 18F, 62Cu, 68Ga, etc.) used in Positron Emission Tomography (PET), and ?–emitters (67Ga, 99mTc, 123I, etc.) used in Single Photon Emission Computed Tomography (SPECT). Radioisotopes used in medicine are produced using both nuclear reactors and cyclotrons.
The 67Ga isotope is one of the main radionuclides produced on cyclotrons and commonly is used in Single-Photon Emission Computed Tomography (SPECT) investigations as a trivalent citrate compound for nuclear medicine imaging, and is a valuable agent in the detection and localization of certain neoplasms and inflammatory lesions. It is well known that when 67Ga is injected into the patient in a citrate form it tends to concentrate in various types of tumours as well as non-malignant lesions. Although it is not a tumour-specific agent, the wide-ranging diagnostic capabilities of the 67Ga radionuclide allow it to be used extensively for the localization of a variety of malignant tumours.
Labeled leukocyte imaging, diagnostics with 67Ga are useful for patients with a Fever of Unknown Origin (FUO), inflammatory bowel disease and, cardiovascular and postoperative infections. It is also useful for differentiating infections from tumor, and for musculoskeletal infections, except in the spine.
A large half-life of the radionuclide 67Ga (78.3 hours) allows conducting studies of metabolic abnormalities of the internal organs of patients. It decays by electron capture and then emits de-excitation gamma-rays that are detected by a gamma camera. 67Ga photopeaks are: 93 keV – 38.81 %, 184 keV – 21.41 %, 300 keV – 16.64%, 393 keV - 4%. Commonly 67Ga is produced by using an enriched 68Zn target through the nuclear reaction 68Zn(p,2n)67Ga in the proton energy range Ep = 20-40 MeV.
The proposed project will explore the possibility of 67Ga isotope production through the reaction 67Zn(p,n)67Ga at proton energy 18 MeV and beam current 30 ?A at the cyclotron C18/18. Within the frame of the project, the production of 67Ga on the targets made from natural and enriched zinc will also be considered.
In a radioisotope production program, nuclear reaction data is mainly needed for the optimization of production routes. Monte-Carlo calculations will be performed for the following purposes:
1. determination of optimal thickness of the targets;
2. selection of the projectile energy range that will maximize the yield of the final product;
3. determination of the parameters of the target to minimize the radioactive impurities;
4. analysis of the contamination by accompanying unwanted products of the reaction.
The technology for the separation of the 67Ga from the zinc target irradiated under the proton beam from the cyclotron C18/18 with energy 18 MeV will be developed. The possible impurities in cases of natural and enriched targets made from zinc will be investigated and evaluated. The methodology for obtaining the gallium citrate will be developed and applied. In the case of enriched targets technique recovery target material for subsequent irradiation after proper chemical treatment will be developed.
To avoid disrupting the technological processes and to exclude the risk of accidents there will be a widely implemented automation at all stages of the production. The project envisages the creation of special facilities to ensure safe storage of the generated radioactive isotopes as well as special vehicles for the transportation of the 67Ga isotopes to consumers.
The first phase of the project will entail a trial production of 67Ga which will then be delivered to the National Center of Radiology and Burns at the Health Ministry of Armenia for clinical testing. For the production of the radioisotopes in accordance to the requirements of the International Atomic Energy Agency (IAEA) and the Armenian Nuclear Regulatory Authority (ANRA), instructions, procedures and regulations on radiation safety and technical operations will be developed. Licenses and certificates for the manufacturing, transportation and supply of isotopes to clinics in Armenia and countries of the region will be obtained from the appropriate national regulatory agencies.
It is expected that as a result of the proposed project, a trial production of 67Ga on the proton beam of cyclotron C18/18 will start. The long half-life of isotope 67Ga will meet the needs of Armenia as well as that of the neighboring countries in the region.
The long half-life of the isotope 67Ga allows to transport it over long distances and to supply them to the clinic in the region.
As potential customers of our product we consider the Caucasus region consisting from Southern Federal District of Russia (population is about 23 millions), Georgia, and the countries of the Middle East.
An important prerequisite for the success of this project is the existing highly qualified personnel of Yerevan Physics Institute (YerPhI) with many years of operational experience in radioactive environments and with high level of safety awareness. A group of technical experts has gained considerable experience and has been successfully involved in the implementation of the following ISTC Projects:
- A-1444 "Development of Medicine Intended Isotopes Production Methods on the Basis of Accelerator Facility of Yerevan Physics Institute” (Manager A.Avetisyan) and;
- A-1785p “Production of Medical Isotopes using Electron Accelerator Facilities” (Manager I.Kerobyan).
Those projects were focused on the development of production methods and technologies of 99mTc and 123I isotopes by photonuclear reactions under the electron linear accelerator at the Yerevan Physics Institute. YerPhI personnel set up a laboratory to separate isotopes from the irradiated target material. The equipment used in these projects included an automatic extractor for the separation of technetium from the molybdenum target as well as equipment to perform quality control on the produced isotopes. However, due to the high primary cost of isotope production on the linear electron accelerator, the industrial production of 99mTc and 123I was not launched.
The goals of present project are:
· Optimization of the proton beam energy range to maximize the isotope yield;
· Optimization of the target parameters to maximize the isotope yield and minimize the impurity;
· Optimization of running conditions and parameters taking into account target temperature conditions;
· Implementation of these methods and technologies in Armenia in order to supply the needs for medical radioisotopes in Armenia as well as neighboring countries as the treatment and health care availability improves in all countries of the region.
· Investigation of new methods and further development of known methods for radionuclide production to be used in nuclear medicine.
· The trial production of 67Ga using the external proton beam from cyclotron C18/18 with proton energy 18 MeV and proton beam current 30 ?A;
The basis for the successful realization of these tasks is:
· The availability of cyclotron C18/18 which is intended for the production of fluorine, and iodine isotopes;
· The presence of experienced personnel that previously worked on the electron accelerator;
· The wide professional experience of the research personnel of the institute.
· The ability to develop and introduce new technological methods, use of the achievements in the field of fundamental physics and in the field of applied sciences.
A significant part of the project participants was formerly involved in the military programs in particular related to the beam weapons programs.
