Optimization and automation of the radiosynthesis of PET ligand targeting Aβ for imaging cerebral amyloid angiopathy

Abstract

Cerebral amyloid angiopathy (CAA) is a common cerebrovascular disorder characterized by the accumulation of beta-amyloid (Aβ) plagues in cerebral blood vessels. A precise diagnosis of CAA is crucial for informing treatment decisions and evaluating the efficacy of therapeutic interventions. We previously reported a novel radiopharmaceutical, [¹⁸F]K10-008, that selectively targets Aβ deposits within the vascular walls of CAA patients. To facilitate its application in clinical settings, we present an optimized labeling protocol for [¹⁸F]K10-008, along with a comprehensive automated synthesis methodology. We systematically evaluated optimal labeling conditions, including the amount of precursor, reaction temperature, various fluorination reaction solvents, and deprotection acids, through laboratory experiments, which were subsequently adapted for automated production using the ALLINONE synthesis module. Our findings demonstrate that clinical doses of [¹⁸F]K10-008 can be produced in a synthesis time of 48 min-48 min and 20 s, achieving exceptional radiochemical purity (>98 %) and an activity yield of 6.73 % ± 1.78 % (decay corrected). Quality control assessments confirmed that all parameters met release criteria. In conclusion, we have successfully produced [¹⁸F]K10-008 with adequate radioactivity and outstanding quality, positioning it for future clinical applications in CAA imaging.

Keywords: Automated synthesis; CAA; F-18; β-Amyloid (Aβ).