N-(4-[18 F]fluorobenzyl)cholylglycine, a novel tracer for PET of enterohepatic circulation of bile acids: Radiosynthesis and proof-of-concept studies in rats

Nuclear Medicine and Biology
Kim FrischRajiv Bhalla

Abstract

Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[18F]fluorobenzyl)cholylglycine ([18F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [18F]FBCGly and a proof-of-concept study by PET/MR in rats. A radiosynthesis of [18F]FBCGly was developed based on reductive alkylation of glycine with 4-[18F]fluorobenzaldehyde followed by coupling to cholic acid. [18F]FBCGly was investigated in vivo by dynamic PET/MR in anesthetized rats; untreated or treated with cholyltaurine or rifampicin. Possible in vivo metabolites of [18F]FBCGly were investigated by analysis of blood and bile samples, and the stability of [18F]FBCGly towards enzymatic de-conjugation by Cholylglycine Hydrolase was tested in vitro. [18F]FBCGly was produced with a radiochemical purity of 96% ± 1% and a non-decay corrected ra...Continue Reading

Citations

Jan 18, 2020·Expert Opinion on Drug Metabolism & Toxicology·Irene Hernández Lozano, Oliver Langer

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