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

Cyclotron production of Ga is a promising approach to supply Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of Ga-DOTATATE prepared from cyclotron-produced Ga was achieved. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with 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. An enriched pressed 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 GaCl 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 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 Ga. The synthesis of 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 monograph on Ga-chloride (accelerator-produced) solution for radiolabeling. Ga-DOTATATE was stable for at least 5 h after formulation. The dosimetry calculated with OLINDA for cyclotron- and generator-produced Ga-DOTATATE was roughly equivalent. The SUV or SUV of tumoral lesions with cyclotron-produced Ga-DOTATATE was equivalent to that with generator-produced Ga. Among physiologic uptake levels, a significant difference was found in kidneys, spleen, and stomach wall, with lower values in cyclotron-produced Ga-DOTATATE in all cases. Integrated cyclotron production achieves reliable high yields of clinical-grade Ga-DOTATATE. The clinical safety and imaging efficacy of cyclotron-produced Ga-DOTATATE in humans provide supporting evidence for its use in routine clinical practice.