Abstract

Synaptic vesicle glycoprotein 2A (SV2A) is a 12-pass transmembrane protein expressed in presynaptic vesicles. Positron emission tomography (PET) imaging of SV2A provides an in vivo measure of synaptic density and has broad applications in the study of neuropsychiatric and neurodegenerative diseases. A fluorine-18-labeled PET tracer targeting SV2A, [18F]SynVesT-1, was originally developed using a copper-mediated fluorination approach that requires initial azeotropic drying of [18F]fluoride with anhydrous acetonitrile. We previously established an efficient radiolabeling strategy in which fluorine-18 retained on an anion-exchange cartridge is eluted as 4-dimethylaminopyridinium [18F]fluoride (DMAPH·[18F]F) by passing a solution of 4-dimethylaminopyridinium trifluoromethanesulfonate (DMAPH·OTf) in dimethylacetamide (DMA), which was directly used in copper-mediated fluorination of various substrates without the need for azeotropic drying. Building on this strategy, we developed a fully automated and reproducible method for the synthesis of [18F]SynVesT-1 using the Trasis All-in-One (AIO) module. The total synthesis time was 60 min, affording a superior overall decay-corrected radiochemical yield (30–37% vs. 20.6 ± 1.2%) while requiring a reduced amount of precursor (2 mg vs. 5 mg) with a radiochemical purity greater than 98%.

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