title: Facile radiosynthesis of fluorine-18 labeled beta-blockers. Synthesis, radiolabeling, and ex vivo biodistribution of [18F]-(2S and 2R)-1-(1-fluoropropan-2-ylamino)-3-(m-tolyloxy)propan-2-ol.
abstract: An efficient and general method has been developed for fluorine-18 labeling of beta-blockers that possess the propanolamine moiety. A new synthetically versatile intermediate, 3-(1-(benzyloxy)propan-2-yl)-2-oxooxazolidin-5-yl)methyl 4-methylbenzenesulfonate (13), was prepared and can be conjugated to any phenoxy core. To demonstrate the synthetic methodology, fluorinated derivatives of toliprolol were prepared, namely, [(18)F]-(2S and 2R)-1-(1-fluoropropan-2-ylamino)-3-(m-tolyloxy)propan-2-ol ((2S and 2R)-[(18)F]1). The radiosyntheses were accomplished in <1 h, with 20-24% (uncorrected for decay, n = 7) radiochemical yields, >96% radiochemical and >99% enantiomeric purities, with specific activities of 0.9-1.1 Ci/micromol (EOS). Ex vivo biodistribution studies with the radiotracers demonstrated excessively rapid washout that may limit their use for cerebral PET imaging.
authors.affiliation: Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 Canada.
authors.forename: Karin A
authors.initials: KA
authors.lastname: Stephenson
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D005462:Fluorine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D011412:Propanolamines / Q000138:chemical synthesis* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C531232:1-(1-fluoropropan-2-ylamino)-3-(3-tolyloxy)propan-2-ol; D000319:Adrenergic beta-Antagonists; D005462:Fluorine Radioisotopes; D011412:Propanolamines