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.
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.
Stephenson
Karin A
KA
Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 Canada.
Wilson
Alan A
AA
Meyer
Jeffrey H
JH
Houle
Sylvain
S
Vasdev
Neil
N
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
C531232:1-(1-fluoropropan-2-ylamino)-3-(3-tolyloxy)propan-2-ol; D000319:Adrenergic beta-Antagonists; D005462:Fluorine Radioisotopes; D011412:Propanolamines