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

Abstract

Cyclotron production of ⁶⁸Ga is a promising approach to supply ⁶⁸Ga radiopharmaceuticals. To validate this capability, an integrated solution for a robust synthesis of ⁶⁸Ga-DOTATATE prepared from cyclotron-produced ⁶⁸Ga was achieved. A retrospective comparison analysis was performed on patients who underwent PET/CT imaging after injection of DOTATATE labeled with ⁶⁸Ga 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. <b>Methods:</b> An enriched pressed ⁶⁸Zn 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 ⁶⁸GaCl₃ 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 ⁶⁸Ga-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 ⁶⁸Ga. <b>Results:</b> The synthesis of ⁶⁸Ga-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 <i>European Pharmacopoeia</i> monograph on ⁶⁸Ga-chloride (accelerator-produced) solution for radiolabeling. ⁶⁸Ga-DOTATATE was stable for at least 5 h after formulation. The dosimetry calculated with OLINDA for cyclotron- and generator-produced ⁶⁸Ga-DOTATATE was roughly equivalent. The SUV_mean or SUV_max of tumoral lesions with cyclotron-produced ⁶⁸Ga-DOTATATE was equivalent to that with generator-produced ⁶⁸Ga. Among physiologic uptake levels, a significant difference was found in kidneys, spleen, and stomach wall, with lower values in cyclotron-produced ⁶⁸Ga-DOTATATE in all cases. <b>Conclusion:</b> Integrated cyclotron production achieves reliable high yields of clinical-grade ⁶⁸Ga-DOTATATE. The clinical safety and imaging efficacy of cyclotron-produced ⁶⁸Ga-DOTATATE in humans provide supporting evidence for its use in routine clinical practice.