Radiosynthesis and preliminary PET evaluation of 18F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1, 2-dihydropyridin-3-yl)benzonitrile for imaging AMPA receptors. Issue 19 (1st October 2016)

• Record Type: Journal Article
• Authors: Yuan, Gengyang; Jones, Graham B.; Vasdev, Neil; Liang, Steven H.
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 19(2016)
• Page Start: 4857
• Page End: 4860
• Publication Date: 2016-10-01
• Subjects: mGluRs metabotropic glutamate receptors -- iGluRs ionotropic glutamate receptors -- NMDA N-methyl-d-aspartate -- AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid -- PET positron emission tomography -- CNS central nervous system -- TEA[18F] [18F]tetraethylammonium fluoride -- SPIAD (1r, 3r, 5r, 7r)-spiro[adamantane-2, 2′-[1, 3]dioxane]-4′, 6′-dione -- RCC radiochemical conversion -- K222 Kryptofix® or 4, 7, 13, 16, 21, 24-Hexaoxa-1, 10-diazabicyclo[8.8.8]hexacosanein -- DMF N, N-dimethylmethanamide -- TMEDA N, N, N′, N′-tetramethylethylenediamine -- DMEDA N, N′-dimethylethylenediamine -- TEAB tetraethylammonium bicarbonate -- SUV standardized uptake value -- RCY radiochemical yield -- DMSO dimethyl sulfoxide -- BBB crossed the blood–brain barrier -- TAC time–activity curve -- ROI region of interest; AMPA receptor -- Positron emission tomography -- Fluorine-18 -- Radiotracer -- Perampanel; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.07.078
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: To prompt the development of 18 F-labeled positron emission tomography (PET) tracers for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, we have prepared 18 F-labeled 2-(1-(3-fluorophenyl)-2-oxo-5-(pyrimidin-2-yl)-1, 2-dihydropyridin-3-yl)benzonitrile ([ 18 F]8 ). The radiosynthesis was achieved by a one-pot two-step method that utilized a spirocyclic hypervalent iodine(III) mediated radiofluorination to prepare the 18 F-labeled 1-bromo-3-fluorobenzene ([ 18 F]15 ) intermediate with K 18 F. A subsequent copper(I) iodide mediated coupling reaction was carried out with 2-(2-oxo-5-(pyrimidin-2-yl)-1, 2-dihydropyridin-3-yl)benzonitrile (10 ) to [ 18 F]8 in 10 ± 2% uncorrected radiochemical yield relative to starting 18 F-fluoride with >99% radiochemical purity and 29.6 ± 7.4 Gbq/μmol specific activity at the time of injection. PET imaging studies with the title radiotracer in normal mice demonstrated good brain uptake (peak standardized uptake value (SUV) = 2.3 ± 0.1) and warrants further in vivo validation.