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

Introduction: The commercially available Ge-68/Ga-68 generators are generally used in clinical context in conjunction with automated or semi -automated modules for the syntheses of Ga-68 radiopharmaceuticals. It is desirable to develop strategies for the formulation of Ga-68-radiopharmaceuticals without use of such expensive modules in order to make Ga-68-based clinical positron emission tomography (PET) more popular and affordable worldwide. Methods: An organic matrix based Ge-68/Ga-68 generator was used for preparation of clinically relevant doses of four different Ga-68-based radiopharmaceuticals, namely Ga-68-DOTA-NOC, Ga-68-NODAGA-RGD(2), Ga-68-PSMA-11 and Ga-68-BPAMD. Detailed performance evaluation of the generator was carried out over the period of 9 months. The radiolabeling conditions were optimized in a hospital radiopharmacy directly utilizing Ga-68 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, Ga-68 could be obtained from the generator in 4 mL of 0.05 M HCl with 60-85% elution yield and >99.99% radionuclidic purity. While directly using Ga-68 eluted from the generator, the Ga-68-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 make Ga-68-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 of Ga-68-based radiopharmaceuticals without using any synthesis module. (C) 2016 Elsevier Inc. All rights reserved.