Clinical 68 Ga-PET: Is radiosynthesis module an absolute necessity?

INTRODUCTION: The commercially available68 Ge/68 Ga generators are generally used in clinical context in conjunction with automated or semi-automated modules for the syntheses of68 Ga radiopharmaceuticals. It is desirable to develop strategies for the formulation of68 Ga-radiopharmaceuticals without use of such expensive modules in order to make68 Ga-based clinical positron emission tomography (PET) more popular and affordable worldwide.

METHODS: An organic matrix based68 Ge/68 Ga generator was used for preparation of clinically relevant doses of four different68 Ga-based radiopharmaceuticals, namely68 Ga-DOTA-NOC,68 Ga-NODAGA-RGD2 ,68 Ga-PSMA-11 and68 Ga-BPAMD. Detailed performance evaluation of the generator was carried out over the period of 9months. The radiolabeling conditions were optimized in a hospital radiopharmacy directly utilizing68 Ga eluted from the generator without use of any synthesis module. Quality control tests of the radiopharmaceuticals were carried out to assess their suitability for clinical use. The clinical utility of the synthesized radiopharmaceuticals was ascertained by performing PET scans in human patients.

RESULTS: During the period of evaluation,68 Ga could be obtained from the generator in 4mL of 0.05M HCl with 60-85% elution yield and >99.99% radionuclidic purity. While directly using68 Ga eluted from the generator, the68 Ga-based radiopharmaceuticals could be prepared with >95% radiochemical purity and they met all the requirements for clinical administration. The clinical efficacy of the radiopharmaceuticals synthesized was established by PET scans in human patients. The performance of the generator remained consistent over the 9-month period and >100 clinical doses of different radiopharmaceuticals were prepared with excellent reproducibility and clinical effectiveness.

CONCLUSIONS: The promising results obtained in this study would make68 Ga-radiopharmacy more practical and cost effective in clinical context. To the best of our knowledge, this is the first report on the clinical scale syntheses and utilization of68 Ga-based radiopharmaceuticals without using any synthesis module.