Synthesis of 18F 4-amino-N-(3-chloro-4-fluorophenyl)-N′-hydroxy-125-oxadiazole-3-carboximidamide (IDO5L): a novel potential PET probe for imaging of IDO1 expression

摘要

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