title: Synthesis of carbon-11-labeled isonicotinamides as new potential PET agents for imaging of GSK-3 enzyme in Alzheimer's disease.
abstract: The authentic standards 2-(cyclopropanecarboxamido)-N-(4-methoxypyridin-3-yl)isonicotinamide (4a) and 2-(cyclopropanecarboxamido)-N-(4-(4-methoxyphenyl)pyridin-3-yl)isonicotinamide (7a), and their corresponding precursors 2-(cyclopropanecarboxamido)-N-(4-hydroxypyridin-3-yl)isonicotinamide (4b) and 2-(cyclopropanecarboxamido)-N-(4-(4-hydroxyphenyl)pyridin-3-yl)isonicotinamide (7b) were synthesized from methyl 2-aminoisonicotinate and cyclopropanecarbonyl chloride with overall chemical yield 47% in three steps, 22% in four steps, 40% in three steps, and 17% in four steps, respectively. The target tracers 2-(cyclopropanecarboxamido)-N-(4-[11C]methoxypyridin-3-yl)isonicotinamide ([11C]4a) and 2-(cyclopropanecarboxamido)-N-(4-(4-[11C]methoxyphenyl)pyridin-3-yl)isonicotinamide ([11C]7a) were prepared from the precursors (4b and 7b) with [11C]CH3OTf through O-[11C]methylation and isolated by HPLC combined with SPE in 40-50% radiochemical yield, based on [11C]CO2and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370-1110GBq/μmol with a total synthesis time of ∼40-min from EOB.
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Mingzhang
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Radiology and Imaging Sciences, Indiana University School of Medicine, 1345 West 16th Street, Room 202, Indianapolis, IN 46202, USA. Electronic address: qzheng@iupui.edu.
authors.forename: Qi-Huang
authors.initials: QH
authors.lastname: Zheng
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007553:Isotope Labeling; D009536:Niacinamide / Q000138:chemical synthesis / Q000737:chemistry* / Q000302:isolation & purification; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification; D052616:Solid Phase Extraction
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D009536:Niacinamide; C027681:isonicotinamide; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer’s disease (AD); Carbon-11-labeled isonicotinamides; Glycogen synthase kinase-3 (GSK-3); Positron emission tomography (PET); Radiosynthesis