Absolute Configuration and an Improved Automated cGMP Production of a Clinically Promising Radiotracer for Imaging...

The vesicular acetylcholine transporter (VAChT), primarily located in presynaptic cholinergic nerve terminals, serves as a key target in neuroimaging studies and neuropathological assessments to quantify cholinergic neuron decline. [¹⁸F]VAT has been demonstrated to serve as a selective and specific radiotracer to quantify VAChT expression in the brains of patients with neurological diseases. Herein, we report the absolute configuration of the chemical structure and development of a straightforward cGMP protocol to produce [¹⁸F]VAT for clinical use. The absolute configuration was unambiguously determined by X-ray crystallography of the VAT phenolic analogue, establishing its (2R,3R) stereochemistry for the first time. The radiotracer production was successfully accomplished using a simple one-pot and one-step approach under cGMP conditions, achieving an average radiochemical yield of 16.9% ± 1.8% (decay-corrected to the end of synthesis), a molar activity of 61.9 ± 19.6% GBq /μmol, with a total synthesis time of approximately 60 minutes (n = 3). The final product met all established quality control criteria for human use.