Scale down and optimized automated production of [68Ga]68Ga-DOTA-ECL1i PET tracer targeting CCR2 expression

Abstract

Abstract Background Recently it has been identified a short peptide that showed allosteric antagonism against C–C motif chemokine receptor 2 (CCR2) expressed on inflammatory monocyte and macrophages. A 7-d-amino acid peptidic CCR2 inhibitor called extracellular loop 1 inverso (ECL1i), d(LGTFLKC) has been identified and labeled to obtain a new probe for positron emission tomography in pulmonary fibrosis, heart injury, abdominal aortic aneurysm inflammation, atherosclerosis, head and neck cancer. Our goal was to develop, optimize and validate an automated synthesis method for [68Ga]68Ga-DOTA-ECL1i to make it available for a broader community. The synthesis of [68Ga]68Ga-DOTA-ECL1i was done using the Scintomics GRP® module with the already estabilished synthesis template for [68Ga]68Ga-DOTATOC/[68Ga]68Ga-PSMA. The radiopharmaceutical production was optimized scaling down the amount of DOTA-ECL1i (from 50 to 10 μg), evaluating synthesis efficiency and relevant quality control parameters in accordance with the European Pharmacopeia. Results Best results were yielded with 20 μg DOTA-ECL1i and then the process validation was carried out by producing three different batches on three different days obtaining an optimal radiochemical yield (66.69%) as well as radiochemical purity (100%) and molar activity (45.41 GBq/µmol). Conclusions [68Ga]68Ga-DOTA-ECL1i was successfully synthesized and it is, thus, available for multi-dose application in clinical settings.