Synthesis and biodistribution of R- and S-isomers of [18F]-fluoropropranolol, a lipophilic ligand for the beta-adrenergic receptor.
The S and R isomers of [18F]-fluoropropranolol (1-[1-fluoro-2-isopropylamino]-3-naphthalen-1-yloxy-propan-2 -ol) have been prepared by reductive alkylation of the appropriate aminoalcohols. The radiosynthesis provides a reasonable yield (approximately 25%) to give products of 99% enantiomeric excess and specific activities of 1-3 Ci/micromol. The dissociation constants for the beta2 adrenergic receptor are 0.5 and 2.5 nM for the S and the R isomers, respectively. The biodistribution data in rats show that uptake and egress of the tracer is rapid but that the result of blocking studies and the difference between the R and the S isomers suggest receptor-mediated uptake in receptor-rich tissue.
Tewson
T J
TJ
Department of Radiology, University of Washington Medical School, University of Washington, Seattle 98195, USA. ttewson@u.washington.edu
Stekhova
S
S
Kinsey
B
B
Chen
L
L
Wiens
L
L
Barber
R
R
D000465:Algorithms; D000818:Animals; D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D007553:Isotope Labeling; D008024:Ligands; D008055:Lipids / Q000737:chemistry; D008297:Male; D011433:Propranolol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000737:chemistry / Q000187:drug effects*; D012995:Solubility; D012997:Solvents; D013237:Stereoisomerism; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D007202:Indicators and Reagents; D008024:Ligands; D008055:Lipids; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; D012997:Solvents; C406244:fluoropropranolol; D011433:Propranolol