title: Microfluidic radiosynthesis and biodistribution of [18 F] 2-(5-fluoro-pentyl)-2-methyl malonic acid.
abstract: 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 [(18) F]-fluorine radiolabeling of the malonic acid derivative, [(18) F] 2-(5-fluoro-pentyl)-2-methyl malonic acid ([(18) F]-FPMA), also known as [(18) F]-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% [(18) F]-fluorine incorporation prior to hydrolysis and purification. Following hydrolysis, the [(18) F]-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 [(18) F]-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.
authors.affiliation: Center for Molecular Imaging, Department of Radiology, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors.forename: Gajanan K
authors.initials: GK
authors.lastname: Dewkar
authors.forename: Gobalakrishnan
authors.initials: G
authors.lastname: Sundaresan
authors.forename: Narottam
authors.initials: N
authors.lastname: Lamichhane
authors.forename: Jerry
authors.initials: J
authors.lastname: Hirsch
authors.forename: Celina
authors.initials: C
authors.lastname: Thadigiri
authors.forename: Thomas
authors.initials: T
authors.lastname: Collier
authors.forename: Matthew C T
authors.initials: MC
authors.lastname: Hartman
authors.forename: Ganesan
authors.initials: G
authors.lastname: Vaidyanthan
authors.forename: Jamal
authors.initials: J
authors.lastname: Zweit
mesh_terms: D000818:Animals; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D007553:Isotope Labeling / Q000379:methods*; D008764:Methylmalonic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D044085:Microfluidics / Q000379:methods*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C532430:5-fluoropentyl-2-methylmalonic acid; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D008764:Methylmalonic Acid
keywords: PET radiochemistry; [18F]-FPMA; [18F]-ML-10; microfluidic technology