Enabling Efficient Positron Emission Tomography (PET) Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) with a Robust and One-Step Radiosynthesis of a Highly Potent 18F-Labeled Ligand ([18F]UCB-H)

We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [F-18] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [F-18]UCB-H ([F-18]7), a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). Over the course of 1 year, 50 automated productions provided 34 +/- 2% of injectable [F-18]7 from up to 285 GBq (7.7 Ci) of [F-18]fluoride in 50 min (uncorrected radiochemical yield, specific activity of 815 +/- 185 GBq/mu mol). The successful implementation of our synthetic strategy within routine, high-activity, and cGMP productions attests to its practicality and reliability for the production of large doses of [F-18]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP F-18-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field.