title: Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor.
abstract: The endothelin-A receptor ligand Atrasentan (ABT-627) was radiolabeled by (11)C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [(11)C]ABT-627 was in the liver, kidneys and lungs. No significant binding was observed in mouse brain or heart. PET studies in a baboon, however, showed accumulation in the myocardium and lungs with a tissue/blood equilibrium reached at 40 min postinjection. Between 35 and 75 min, the heart/blood and lung/blood ratios were 1.72 and 1.31, respectively. Pretreatment with a 0.39 mg/kg dose of unlabeled ABT-627 inhibited the uptake of the tracer by 53-54% in both the myocardium and lungs at 65 min.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. bmathews@petscan.nm.jhu.edu
authors.forename: William B
authors.initials: WB
authors.lastname: Mathews
authors.forename: Tamas G
authors.initials: TG
authors.lastname: Zober
authors.forename: Hayden T
authors.initials: HT
authors.lastname: Ravert
authors.forename: Ursula
authors.initials: U
authors.lastname: Scheffel
authors.forename: John
authors.initials: J
authors.lastname: Hilton
authors.forename: Darryl
authors.initials: D
authors.lastname: Sleep
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dannals
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szabo
mesh_terms: D000818:Animals; D000077868:Atrasentan; D002250:Carbon Radioisotopes; D005240:Feasibility Studies; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009928:Organ Specificity; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D044022:Receptor, Endothelin A / Q000378:metabolism*; D013045:Species Specificity; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D044022:Receptor, Endothelin A; D000077868:Atrasentan