Preparation Method, Quality Control, and Stability Studies of the Radiopharmaceutical Gallium [68Ga]Ga-edotreotide

ABSTRACTPurpose: Gallium-68-based radiopharmaceuticals are widely employed in Nuclear Medicine forPET/CT imaging, particularly in the diagnosis, staging, and monitoring of neuroendocrine tumors(NETs). This study focuses on the evaluation of the radiochemical and chemical purity of Gallium[68Ga]Ga-edotreotide, also known as [68Ga]Ga-DOTA-TOC, to determine its valid shelf-lifefollowing the end of synthesis (EOS).Methods: The stability study was carried out in accordance with Chapter 10 of the GoodPreparation Guidelines for Radiopharmaceuticals, under both standard and "worst-case"conditions. All analytical methods complied with the specifications of the European PharmacopoeiaMonograph 01/2022:2482 (Ph. Eur.), Gallium (68Ga) edotreotide injection.Results: Under standard conditions, [68Ga]Ga-edotreotide maintained a radiochemical purityabove the threshold specified by the European Pharmacopoeia (≥ 95%) up to 3 hours post-EOS.At 4 hours, purity dropped below the specification limits. The assessment of chemical purityconfirmed these findings, with impurities exceeding limits at the 4-hour mark. Under "worst-case"storage conditions, a similar stability pattern was observed for samples stored in plastic syringesand those subjected to mild heating (30°C and 40°C). However, for samples stored underrefrigerated conditions at 4°C, radiochemical purity dropped below the acceptable limit as early as3 hours after synthesis.Conclusion: The radiopharmaceutical [68Ga]Ga-edotreotide prepared using an automatedsynthesis module is stable for up to 3 hours after synthesis. No significant differences in stabilityare observed between storage in glass vials and plastic syringes. While exposure to mild heatingup to 40°C does not alter the product quality, refrigeration at 4°C prematurely compromises thecomplex structure and radiochemical purity. Keywords: Radiopharmaceuticals, [68Ga]Ga-edotreotide, Synthesis, Quality Control,Stability Study, Neuroendocrine Tumors, HPLC.