Microfluidic radiosynthesis and biodistribution of [18F] 2-(5-fluoro-pentyl)-2-methyl malonic acid

Microfluidics technology has emerged as a powerful tool for the radiosynthesis of positron emission tomography (PET) and single‐photon emission computed tomography radiolabeled compounds. In this work, we have exploited a continuous flow microfluidic system (Advion, Inc., USA) for the [18F]‐fluorine radiolabeling of the malonic acid derivative, [18F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid ([18F]‐FPMA), also known as [18F]‐ML‐10, a radiotracer proposed as a potential apoptosis PET imaging agent. The radiosynthesis was developed using a new tosylated precursor. Radiofluorination was initially optimized by manual synthesis and served as a basis to optimize reaction parameters for the microfluidic radiosynthesis. Under optimized conditions, radio‐thin‐layer chromatography analysis showed 79% [18F]‐fluorine incorporation prior to hydrolysis and purification. Following hydrolysis, the [18F]‐FPMA was purified by C18 Sep‐Pak, and the final product was analyzed by radio‐HPLC (high‐performance liquid chromatography). This resulted in a decay‐corrected 60% radiochemical yield and ≥98% radiochemical purity. Biodistribution data demonstrated rapid blood clearance with less than 2% of intact [18F]‐FPMA radioactivity remaining in the circulation 60 min post‐injection. Most organs showed low accumulation of the radiotracer, and radioactivity was predominately cleared through kidneys (95% in 1 h). Radio‐HPLC analysis of plasma and urine samples showed a stable radiotracer at least up to 60 min post‐injection. Microfluidic radiosynthesis of [18F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid ([18F]‐FPMA), using a new derivative of the tosylate precursor, diethyl 2‐methyl‐2‐(5‐tosyloxy)pentyl malonate, has been developed. Optimization of manual synthesis has been translated to the development of a high activity microfluidic radiosynthesis of [18F]‐FPMA in order to accelerate translational research studies of this radiotracer.