Synthesis of [F-18] 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L): a novel potential PET probe for imaging of IDO1 expression

摘要

To synthesize F-18-labeled positron emission tomography (PET) ligands, reliable labeling techniques inserting F-18 into a target molecule are necessary. The F-18-fluorobenzene moiety has been widely utilized in the synthesis of F-18-labeled compounds. The present study utilized [F-18]-labeled aniline as intermediate in [F-18]-radiolabeling chemistry for the facile radiosynthesis of 4-amino-N-(3-chloro-4-fluorophenyl)-N-hydroxy-1,2,5-oxadiazole-3-carboximidamide ([F-18]IDO5L) as indoleamine 2,3-dioxygenase 1 (IDO1) targeted tracer. IDO5L is a highly potent inhibitor of IDO1 with low nanomolar IC50. [F-18]IDO5L was synthesized via coupling [F-18]3-chloro-4-fluoroaniline with carboximidamidoyl chloride as a potential PET probe for imaging IDO1 expression. Under the optimized labeling conditions, chemically and radiochemically pure (>98%) [F-18]IDO5L was obtained with specific radioactivity ranging from 11 to 15GBq/mu mol at the end of synthesis within 90min, and the decay-corrected radiochemical yield was 18.2 +/- 2.1% (n=4).