(68)Ga-DOTATATE Prepared from Cyclotron-Produced (68)Ga: An Integrated Solution from Cyclotron Vault to Safety Assessment and Diagnostic Efficacy in Neuroendocrine Cancer Patients

Cyclotron production of (68)Ga is a promising approach to supply (68)Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of (68)Ga-DOTATATE prepared from cyclotron-produced (68)Ga was achieved. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with (68)Ga produced by a cyclotron or eluted from a generator to demonstrate the clinical safety and diagnostic efficacy of the radiopharmaceutical as a routine standard-of-care diagnostic tool in the clinic. Methods: An enriched pressed (68)Zn target was irradiated by a cyclotron with a proton beam set at 12.7 MeV for 100 min. The fully automated process uses an in-vault dissolution system in which a liquid distribution system transfers the dissolved target to a dedicated hot cell for the purification of (68)GaCl(3) and radiolabeling of DOTATATE using a cassette-based automated module. Quality control tests were performed on the resulting tracer solution. The internal radiation dose for (68)Ga-DOTATATE was based on extrapolation from rat biodistribution experiments. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with cyclotron- or generator-produced (68)Ga. Results: The synthesis of (68)Ga-DOTATATE (20.7 ± 1.3 GBq) with high apparent molar activity (518 ± 32 GBq/μmol at the end of synthesis) was completed in 65 min, and the radiopharmaceutical met the requirements specified in the European Pharmacopoeia monograph on (68)Ga-chloride (accelerator-produced) solution for radiolabeling. (68)Ga-DOTATATE was stable for at least 5 h after formulation. The dosimetry calculated with OLINDA for cyclotron- and generator-produced (68)Ga-DOTATATE was roughly equivalent. The SUV(mean) or SUV(max) of tumoral lesions with cyclotron-produced (68)Ga-DOTATATE was equivalent to that with generator-produced (68)Ga. Among physiologic uptake levels, a significant difference was found in kidneys, spleen, and stomach wall, with lower values in cyclotron-produced (68)Ga-DOTATATE in all cases. Conclusion: Integrated cyclotron production achieves reliable high yields of clinical-grade (68)Ga-DOTATATE. The clinical safety and imaging efficacy of cyclotron-produced (68)Ga-DOTATATE in humans provide supporting evidence for its use in routine clinical practice.