title: A novel beta-adrenoceptor ligand for positron emission tomography: evaluation in experimental animals.
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.
authors.affiliation: Positron Emission Tomography Center, University Hospital, Groningen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: van Waarde
authors.forename: P H
authors.initials: PH
authors.lastname: Elsinga
authors.forename: P
authors.initials: P
authors.lastname: Doze
authors.forename: M
authors.initials: M
authors.lastname: Heldoorn
authors.forename: K A
authors.initials: KA
authors.lastname: Jaeggi
authors.forename: W
authors.initials: W
authors.lastname: Vaalburg
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics; D000818:Animals; D001562:Benzimidazoles / Q000097:blood / Q000493:pharmacokinetics; D002247:Carbon Isotopes; D005069:Evaluation Studies as Topic; D008024:Ligands; D008297:Male; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D014055:Tomography, Emission-Computed
chemical_list: D000319:Adrenergic beta-Antagonists; D001562:Benzimidazoles; D002247:Carbon Isotopes; D008024:Ligands; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; C109239:CGP 12388