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 11C-methylaton of the desmethyl precursor in phenolate form. In mice, the highest uptake of [11C]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.