Rapid Production of PET Brain Ligands using Self Optimizing Microchemistry

DESCRIPTION (provided by applicant): The NIH has expressed a need for focused development of PET and SPECT brain ligands as well as research and development of new technologies for radiotracer production to aid in animal and human drug research. PET compounds are powerful imaging tools, but are often difficult and slow to produce. By applying high speed microfluidic techniques, multiple PET brain ligands can be produced rapidly at significantly reduced cost and will be demonstrated in Phase I with 6-[18F]Fluorodopa. 6-[18F]Fluorodopa is an [18F]labeled biomarker for imaging the dopaminergic system function and is a useful neuro imaging tool. It also has a DSP monograph allowing PET radioisbtope production facilities to make and sell 6- [18F]Fluorodopa, however, the complex synthesis is costly, slow, and gives low yields. Typical production is via electrophilic fluorination using [18F]F2 which requires a gas target and cryo trapping that further complicates the production and availability. In collaboration with DC Davis, NanoTek proposes development of a high speed nucleophilic 6-[18F]Fluorodopa synthesis using a microfluidic reactor. Building on demonstrated results for [18F]FDG, we predict production of 6-[18F]Fluorodopa in approximately 2 minutes at yields of >50% compared to conventional methods that take 120 minutes with yields of 5% to 25%. We will develop a three step reaction process with intermediate and final purification that can be performed on a small plug in cartridge. The automated high speed process will make accessibility to 6-[18F]Fluorodopa commonplace and reduce the cost from current rates of $2500 per dose to something comparable with [18F]FDG at approximately $250 per dose. Phase I efforts for this special call STTR will design, build and test the multi-step reactor device for the synthesis of 6-[18F]Fluorodopa including flow-based intermediate purification. Phase II will incorporate final product HPLC purification and closed-loop continuous flow optimization of the reaction process. Phase II will also demonstrate efficacy of the compound using MicroPET at the Center for Molecular and Genomic Imaging at UC Davis.