Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications

Cyclotron production of Tc-99m is a promising route to supply Tc-99m radiopharmaceuticals. Higher Tc-99m yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of Tc-99m produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required. Methods: Thick Mo-100 (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate Tc-99m was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using gamma-ray spectrometry. The internal radiation dose for Tc-99m-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms. Results: Extracted sodium pertechnetate Tc-99m met all provisional quality standards. The formulated solution for injection had a pH of 5.0-5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of Tc-99m produced with 99.03% enriched Mo-100 was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of Tc-99m produced with 99.815% enriched Mo-100 was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to Tc-99m without any radionuclidic impurities was below 10% for sodium pertechnetate Tc-99m produced from 99.03% Mo-100 if injected up to 6 h after the EOB. For 99.815% Mo-100, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced Tc-99m were equivalent to those obtained with Tc-99m eluted from a conventional generator. Conclusion: Clinical-grade sodium pertechnetate Tc-99m was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced Tc-99m in routine clinical practice.