A novel beta-adrenoceptor ligand for positron emission tomography: evaluation in experimental animals

European Journal of Pharmacology
A Van WaardeW Vaalburg

Abstract

Myocardial and pulmonary beta-adrenoceptors can be imaged and quantified with the antagonist (S)-4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-b enzimidazol-2-[11C]-one (S-[11C]CGP-12177). The synthesis of this ligand (based on the reaction of a precursor with [11C]phosgene) is laborious and in many centers the final product has a low and variable specific activity. This prevents widespread use of S-[11C]CGP-12177 for studies in patients. We prepared S-[11C]CGP-12388, the isopropyl analogue of CGP-12177, by a reliable one-pot procedure and evaluated the radiopharmaceutical for beta-adrenoceptor imaging. Blocking experiments with subtype-selective beta-adrenergic drugs showed that myocardial and pulmonary uptake of S-[11C]CGP-12388 in anesthetized rats reflects ligand binding to beta1- and beta2-adrenoceptors. In this animal model, clearance, metabolism and tissue/plasma ratios of S-[11C]CGP-12388 were similar to those of S-[11C]CGP-12177. A [18F]fluoroisopropyl analogue of CGP-12177 showed less favorable characteristics. S-[11C]CGP-12388 was therefore selected for evaluation in humans and it may become the tracer of choice for clinical studies since it is easily prepared.

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Citations

May 5, 2007·European Journal of Nuclear Medicine and Molecular Imaging·Riikka LautamäkiFrank M Bengel
Apr 4, 2002·Nuclear Medicine and Biology·K NishijimaN Tamaki
Sep 2, 2006·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·K Nishijima
Sep 11, 2004·Assistive Technology : the Official Journal of RESNA·Jon A SanfordTina Butterfield
Nov 3, 2004·CNS Spectrums·J McConathyM M Goodman
Jun 18, 2020·Nuclear Medicine and Biology·Toshimitsu FukumuraMing-Rong Zhang

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