title: (18)F-Fluorodeoxyglucamines: Reductive amination of hydrophilic (18)F-fluoro-2-deoxyglucose with lipophilic amines for the development of potential PET imaging agents.
abstract: Maillard reaction of (18)F-FDG with biological amines results in the formation of (18)F-fluorodeoxyglycosylamines ((18)F-FDGly) as pseudo-Amadori products. To increase in vivo stability, we report the reductive amination of FDGly to provide reduced fluorodeoxyglucamines (FDGlu). (18)F-Fluorodeoxyglucamines ((18)F-FDGlu), resulting from linking (18)F-FDG (hydrophilic) to lipophilic molecules containing amine group may be useful as positron emission tomography (PET) imaging agents. Two amine derivatives, 7-chloro-8-hydroxy-3-methyl-l-(3'-aminophenyl)-2,3,4,5-tetrahydro-lH-3-benzazepine (SCH 38548 for dopamine D1 receptors) and BTA-0 (for Aβ amyloid) were reacted with FDG under reductive amination conditions to yield stable products, FDGluSCH and FDGluBTA. FDGluSCH had high binding affinity to rat brain dopamine D1 receptors with a Ki of 19.5 nM while FDGluBTA had micromolar affinity for human frontal cortex Aβ plaques. (18)F-FDGluSCH was prepared in low to modest radiochemical yields and preliminary results showed binding to the rat striatum in brain slices. In vivo stability of(18)F-FDGluSCH needs to be determined. Our results suggest that (18)F-FDG is a useful 'radioactive synthon' for PET radiotracer development. Its usefulness will have to be determined on the basis of the structure-activity relationship of the target molecule.
authors.affiliation: Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, United States.
authors.forename: Aparna
authors.initials: A
authors.lastname: Baranwal
authors.affiliation: Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, United States. Electronic address: j.mukherjee@uci.edu.
authors.forename: Jogeshwar
authors.initials: J
authors.lastname: Mukherjee
mesh_terms: D000586:Amination; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D019788:Fluorodeoxyglucose F18 / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D010084:Oxidation-Reduction; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000032:analysis*
chemical_list: D000588:Amines; D019275:Radiopharmaceuticals; D017447:Receptors, Dopamine D1; D019788:Fluorodeoxyglucose F18
keywords: (18)F-FDG; (18)F-Fluorodeoxyglucamine; Dopamine D1 receptor; Imaging; PET