title: Synthesis of [(18) F] 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.
abstract: To synthesize (18) F-labeled positron emission tomography (PET) ligands, reliable labeling techniques inserting (18) F into a target molecule are necessary. The (18) F-fluorobenzene moiety has been widely utilized in the synthesis of (18) F-labeled compounds. The present study utilized [(18) F]-labeled aniline as intermediate in [(18) F]-radiolabeling chemistry for the facile radiosynthesis of 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide ([(18) F]IDO5L) as indoleamine 2,3-dioxygenase 1 (IDO1) targeted tracer. IDO5L is a highly potent inhibitor of IDO1 with low nanomolar IC50 . [(18) F]IDO5L was synthesized via coupling [(18) F]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%) [(18) F]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).
authors.affiliation: Department of Cancer Imaging and Metabolism, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Gillies
authors.forename: Haibin
authors.initials: H
authors.lastname: Tian
mesh_terms: D000818:Animals; D005240:Feasibility Studies; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008422:Materials Testing; D057054:Molecular Imaging / Q000379:methods*; D015336:Molecular Probe Techniques; D015335:Molecular Probes / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
chemical_list: D005462:Fluorine Radioisotopes; D015335:Molecular Probes; D010069:Oxadiazoles; D019275:Radiopharmaceuticals
keywords: 3-dioxygenase; IDO1; PET imaging; fluorine-18; indoleamine 2; radiolabeling