Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor.
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.
Mathews
William B
WB
Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA. bmathews@petscan.nm.jhu.edu
Zober
Tamas G
TG
Ravert
Hayden T
HT
Scheffel
Ursula
U
Hilton
John
J
Sleep
Darryl
D
Dannals
Robert F
RF
Szabo
Zsolt
Z
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
D002250:Carbon Radioisotopes; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D044022:Receptor, Endothelin A; D000077868:Atrasentan