A tale of three targets: Direct, multi-Curie production of ^99mTc on three different cyclotrons

Objectives Many of the >950 medical cyclotrons around the world today operate between 16 and 24 MeV, an ideal range for the production of ^99mTc via the ¹⁰⁰Mo(p,2n) reaction.¹ Since 2010, our consortium has been studying the parameters for producing ^99mTc on three different cyclotron models: A PETtrace (at 16.5 MeV), a TR19 and more recently a TR30 (at 24 MeV).² Here we report the target hardware configuration, irradiation parameters and GMP purification of ^99mTc under the operational capabilities of each machine.

Methods Irradiations were performed on enriched ¹⁰⁰Mo solid targets, manufactured using either electrophoretic deposition (TR19, TR30) or press-sinter-braze (PETtrace) protocols.^3,4 Up to 6 hr irradiations using 16, 18 and 24 MeV protons with currents ranging from 130 (PETtrace) to 450 µA (TR30) were used. Irradiated targets were dissolved with H₂O₂ and purified on an automated system (Trasis) using a crosslinked PEG resin.^{5 99m}TcO₄ was eluted in 0.9% NaCl and examined for radionuclidic and radiochemical purity and used as a feedstock for kit formulations. Preclinical biodistribution studies were performed to establish bioequivalence between cyclotron and generator-produced ^99mTcO₄.

Results ^99mTc production yields followed theoretical predictions,⁶ producing ~4.7 Ci (174 GBq) on the PETtrace to more than 30 Ci (1.1 TBq) on the TR30 (at 24 MeV). Reconstituted kits passed standard QC tests. Final radionuclidic purity depended on beam energy and the isotopic composition of the target material. Only Tc was present in the final solution, with ^93m,gTc, ^94m,gTc, ^95m,gTc, ⁹⁶Tc and ^97mTc as the key contaminants.

Conclusions We have developed a practical and versatile system for routine production of large quantities of ^99mTcO₄ using a variety of available cyclotrons. Irradiations provided a final product suitable for standard ^99mTc kit reconstitution and radionuclidic purity commensurate with marginal additional patient dose.⁷ All data acquired to date support an imminent clinical trial.

Research Support The authors wish to thank Natural Resources Canada and our respective institutions for funding.