Production Of 99mTc Research Articles

Investigation of alternative production routes of 99mTc: deuteron induced reactions on 100Mo

Activation cross sections of deuteron induced nuclear reactions on enriched (100)Mo have been studied up to 50 MeV using the stacked foil irradiation technique and gamma spectroscopy. The excitation functions for production of (99m)Tc, (ind99)Mo, (ind98m)Nb, (ind97mg)Nb radioisotopes were measured for the first time and compared with the results of the ALICE-D, EMPIRE-D and TALYS codes. Production possibilities of the medically important (99m)Tc are discussed.

Cyclotron production of medium-lived NCA technetium radiotracers: use for biodistribution studies and setting up new 99mTc production methods

Cyclotron production of medium-lived NCA technetium radiotracers: use for biodistribution studies and setting up new 99mTc production methods

Technetium-99m in production and use

Several types of generators have been developed for the production of 99mTc. Due to its excellent performances, the chromatographic type, based on the fission-produced 99Mo sorbed in alumina, is predominant. Technetium-99m is obtained in the form of sodium pertechnetate-99mTc. However, due to the known disadvantages of the production of (n, f)99Mo, attempts are made to avoid uranium fission. The technologies based on (n, g)99Mo (sublimation, extraction, gel) are, with the exception of the gel generator, of limited importance. Certain nuclear reactions in cyclotrons can produce 99Mo (or directly 99mTc) but the obtained results are still not satisfying. Technetium-99m is used in the form of radiopharmaceuticals which are prepared by addition of 99mTc-eluate to the inactive components comprised in the 'cold' kits. The chromatographic (n, f)99Mo/99mTc generator and several 99mTc-radiopharmaceuticals have been developed and are regularly produced in the Vinca Institute of Nuclear Sciences (Laboratory for Radioisotopes).

Analysis of Radioactive Wastes Formed as a Result of the Production of99mTc on the Basis of Irradiated Molybdenum Trioxide Using a Centralized Generator as a Base

The radioactive wastes formed as a result of the production of 99mTc by the zirconium–molybdenum gel technology are studied. It is shown that high-activity isotopes are not formed when a MoO3 target is irradiated; there are no gaseous and solid wastes. The activity of the liquid wastes is due to spent 99Mo and short-lived 99mTc; after the 99Mo decays, they can be removed as ordinary water solutions. Therefore, this technology for obtaining 99mTc is waste-free from the standpoint of radiation.

Obtaining molybdenum-99 in the IRT-T research reactor using resonance neutrons

The yield of 99Mo from the 98Mo(n,γ) 99Mo reaction significantly depends of the energy spectrum of the neutron flux. It is well known that the cross-section for this reaction is about 130 mb, whereas the resonance integral of the reaction is 6.9 b. The aim of this work was to investigate the conditions that let to increase 99Mo yield from the targets with natural and enriched isotope composition under irradiation by resonance neutrons at the IRT-T research reactor. The calculations of integrated cross-sections of all Mo isotopes in the region of the 98Mo resonances showed that screening in the target with natural isotope composition by other isotopes is relatively small. So the 98Mo in the natural mixture can be activated by resonance neutrons approximately in the same manner as pure 98Mo. Experimental measurements of the 98Mo(n,γ) effective cross-section using the MoO 3 sample with natural and enriched composition in the reactor channels with the beryllium moderator with the thickness of 20 up to 90 mm showed that the effective cross-sections in these channels reach the value of 700 mb. The contribution of the epithermal neutrons into the 98Mo activity was 68% for the enriched targets and 78% for natural molybdenum, respectively. At that channel it is possible to produce 99Mo with specific activity up to 3.4 Cu/g with samples of natural isotope composition and up to 15 Cu/g with enriched samples on the base of reactors with neutron flux of (1.7 × 10 14 n/(cm 2 s)). Such 99Mo specific activity is enough not only to realize extraction technologies production of 99mTc, but to manufacture sorption generators of 99mTc without wastes.

Evaluation of proton induced reactions on 100Mo: New cross sections for production of 99mTc and 99Mo

The use of the 99Mo→99mTc generator in nuclear medicine is well established world wide. The production of the 99Mo (T1/2 = 66 h) parent as a fission product of 235U is largely based on the use of reactor technology. From the early 1990's accelerator based production methods to provide either direct produced 99mTc or the parent 99Mo, were studied and suggested as potential alternatives to the reactor based production of 99Mo. A possible pathway for the charged particle production of 99mTc and 99Mo is irradiation of molybdenum metal with protons via the reaction 100Mo(p,2n)99mTc and 100Mo(p,pn)99Mo, respectively. The earlier published excitation functions show large differences in their maximum that result in large differences in the calculated yields. We therefore decided to study the excitation function for these proton-induced reactions. In this work the newly measured excitation functions as well as an evaluation of earlier measured data and a discussion of the observed disagreements are presented.

Alice predictions on the accelerator production of molybdenum-99

The ALICE code was used to calculate the excitation functions for proton induced reactions on 100Mo that lead to the production of Nb, Mo and Tc isotopes. The ALICE code predicts a maximum cross section of the order of 100 mb for the 100Mo(p,pn) 99Mo nuclear reaction. ALICE predicts that the production of a few Curies of 99Mo is feasible if high intensity (mA) protons are degraded from 50→30 MeV in a target of highly isotopically enriched 100Mo. The ALICE code cannot be used to predict the cross sections for the isomeric states for the 100Mo(p, 2p) 99m+gNb→ 99Mo reactions. However, the predicted cross section for protons on 100Mo to yield 99Nb suggests that the (p,2p) reaction channel does not contribute significantly to the thick target yield of 99Mo. Several considerations suggest that accelerator production of 99Mo→ 99mTc generators is not a practical economic alternative to fission produced 99Mo. Considerations for the cyclotron production of 99mTc are discussed.

Excitation functions for the cyclotron production of 99mTc and 99Mo

Excitation functions for the 100Mo(p,2n) 99mTc, 100Mo(p,pn) 99Mo and 98Mo(p,γ) 99mTc nuclear reactions were determined using 97.4 and 99.5% isotopic enrichment of 100Mo and 98Mo, respectively. The irradiations were performed on three different cyclotrons with overlapping data points from 6 to 65 MeV. The optimum energy range for the 100Mo(p,2n) 99mTc reaction is 22→12 MeV with a peak at ∼17 MeV and maximum cross section of ∼200 mb. Over this energy range the production yield of 99mTc amounts to 11.2 mCi (415 MBq)/μA h or 102.8 mCi (3804 MBq)/μA at saturation. There is no serious radionuclidic impurity problem. Production of 99Mo is not viable due to the low cross section (∼130 mb) over the proton energy range of 30 to 50 MeV. The 98Mo(p,γ) 99mTc reaction was found to have a cross section of <0.2 mb over the proton energy range studied. The earlier assignment of this reaction channel as a potential route for production of 99mTc with a medical cyclotron is refuted in this study. Countries that do not have access to fission molybdenum-99 for the 99Mo→ 99mTc generator, could consider use of a >17 MeV proton energy cyclotron for regional production of 99mTc.

A System of 99mTc Production Based on Distributed Electron Accelerators and Thermal Separation

A system has been developed for the production of 99mTc based on distributed electron accelerators and thermal separation. The radioactive decay parent of 99mTc, 99Mo, is produced from 100Mo by a photoneutron reaction. Two alternative thermal separation processes have been developed to extract 99mTc. Experiments have been performed to verify the technical feasibility of the production and assess the efficiency of the extraction processes. A system based on this technology enables the economical supply of 99mTc for a large nuclear pharmacy. Twenty such production centers distributed near major metropolitan areas could produce the entire U.S. supply of 99mTc at a cost less than the current subsidized price.

The continuing important role of radionuclide generator systems for nuclear medicine.

In this review, the continuing importance and status of development of radionuclide generator systems for nuclear medicine are discussed. Radioisotope costs and availability are two important factors, and both nuclear reactors and accelerator facilities are required for production of the parent radioisotopes. Radionuclide generator research is currently focused on the development of generators which provide radioisotopes for positron emission tomography (PET) applications and daughter radioisotopes for various therapeutic applications which decay primarily by particle emission. Generator research continues to be influenced by developments and requirements of complementary technologies, such as the increasing availability of PET. In addition, the availability of a wide spectrum of tumor-specific antibodies, fragments, and peptides for radioimmunodiagnosis and radioimmunotherapy has stimulated the need for generator-derived radioisotopes. The advantages of treatment of arthritis of the synovial joints with radioactive particles (radiation synovectomy) may be expected to be of increasing importance as the elderly population increases, and many of these agents are prepared using generator-derived radioisotopes such as yttrium-90 and rhenium-188. Therapeutic use of the "in vivo generator" is a new approach, where the less radiotoxic parent radioisotope is used to prepare tissue-specific therapeutic agents. Following in vivo site localization, decay of the parent provides the daughter for therapy at the target site. The principal foundation of most diagnostic agents will continue to require technetium-99m from the molybdenum-99/technetium-99m ("Moly") generator. With the limited availability of nuclear reactors and facilities necessary for production and processing of fission 99mTc and the significant issues and problems associated with radioactive waste processing, however, the possibility of utilizing lower specific activity 99Mo produced from neutron activation of enriched 98Mo may become practical in the future.

Integral cross section of the99Tc(γ,γ′)99mTc reaction at 4 MeV

99mTc production was studied with the aid of photoexcitation by a 4 MeV endpoint energy bremsstrahlung from the LINAC of the Institute of Isotopes, Budapest. The intensity of the γ-flux was monitored by disc-shaped natural indium plates, placed in front of and behind the small cylindrical aluminium holders containing TcO2 samples in a powder form. Isomeric activities were measured through the 140 keV γ-line by a Ge spectrometer. The integral cross section at 4 MeV was found to be 63.3±7.1 μbMeV, which can be considered reasonable compared to the corresponding value of 55.3 μbMeV established for the115In (γ,γ′)115mIn reaction. We also attempted the photoexcitation of99mTc by irradiation with γ-rays from a 1.5×1015 Bq60Co source, but no isomeric activity could be observed. This places the first activation level between 1.33 and 4 MeV.

Radionuclide production with > 70-MeV proton accelerators: current and future prospects

The role of proton accelerators (i.e. cyclotrons) in the production of medical radionuclides is increasing as a result of new trends in medical research and due to clinical needs associated with the expanding field of positron emission tomography (PET). Accelerators also produced radionuclides needed in single photon emission computerized tomography (SPECT). Modern high-intensity H − cyclotrons are now commercially available, allowing the use of simultaneous beams, as well as a highly reliable operation. Furthermore, new accelerator-based methods for the production of several useful positron emitters and for the large-scale production of 99mTc and 99Mo, are being investigated. Based on new data, an ample supply for both PET and SPECT radiopharmaceuticals is feasible and may be obtained from centralized regional facilities operating a modern accelerator. For these facilities, an accelerator capable of delivering > 70-MeV protons is, by far, the best overall choice. This rationale is explained here and supported with a summary of radionuclide production data. An increasing role for modern proton accelerators in nuclear medicine and other applications is believed to be scientifically proven and forthcoming although further research and development of the technical and economical basis are required.

Cyclotron production of NCA 99mTc and 99Mo. An alternative non-reactor supply source of instant 99mTc and 99Mo→ 99mTc generators

The direct production of no-carrier-added (NCA) 6.02 h 99mTc and of 66 h 99mMo using proton beams on natural Mo targets was investigated. The major objective of this work was to evaluate the potential of utilizing high-intensity proton accelerators as a supply source of 99mTc and 99Mo for use in diagnostic nuclear medicine. The excitation functions for the production of the directly-made 99mTc via the 100Mo(p, 2n) 99mTc ( Q = −7.85 MeV) reaction, and of its parent 99Mo via the 100Mo(p, pn) 99Mo ( Q = −8.30 MeV) and 100 Mo(p, 2 p) 99 m Nb(15 s) → 99 Mo (Q = −11.14 MeV) reactions, were measured the 68-8 MeV energy range. Single and cumulative yields for 99mTc and 99Mo, and for other Tc, Mo, Zr, Nb and Y radiocontaminants were also determined. The prospects of integrating the use of enriched 100Mo targets with high-intensity, dual beam, H − accelerators was analyzed. The potential of this combined method to replace or complement the current reactor-based supply sources of 99Mo→ 99mTc generators, is also discussed. Finally, a brief analysis is made on the potential use of this combined technology to support the anticipated expansion of nuclear medicine in developing nations.

Application possibilities of a new generator concept for99mTc production by means of the Triga-Mark III reactor in Mexico

A new concept of prefabricated99mTc generator has been experimentally tested as a possible procedure for local production of99mTc for medical purposes by means of the ININ-Salazar /Mexico/ Triga-Mark III reactor working at 1 MW.