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Microfluidic radiosynthesis and biodistribution of [ 18 F] 2‐(5‐fluoro‐pentyl)‐2‐methyl malonic acid
Author(s) -
Dewkar Gajanan K.,
Sundaresan Gobalakrishnan,
Lamichhane Narottam,
Hirsch Jerry,
Thadigiri Celina,
Collier Thomas,
Hartman Matthew C. T.,
Vaidyanthan Ganesan,
Zweit Jamal
Publication year - 2013
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3016
Subject(s) - radiosynthesis , biodistribution , chemistry , radiochemistry , malonic acid , high performance liquid chromatography , hydrolysis , positron emission tomography , chromatography , nuclear chemistry , organic chemistry , nuclear medicine , biochemistry , medicine , in vitro
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.