Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

Mathews, William B.; Zober, Tamas G.; Ravert, Hayden T.; Scheffel, Ursula; Hilton, John; Sleep, Darryl; Dannals, Robert F.; Szabo, Zsolt

doi:10.1016/j.nucmedbio.2005.07.012

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 1 , Pages 15-19, January 2006

Synthesis and in vivo evaluation of a PET radioligand for imaging the endothelin-A receptor

William B. Mathews
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
- Corresponding author. Tel.: +1 410 614 0110; fax: +1 410 614 0111.
Tamas G. Zober
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
Hayden T. Ravert
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
Ursula Scheffel
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
John Hilton
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
Darryl Sleep
- Abbott Laboratories, Abbott Park, IL 60064, USA
Robert F. Dannals
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
Zsolt Szabo
- Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA

Received 7 February 2005; received in revised form 27 July 2005; accepted 29 July 2005.

Abstract

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.

Keywords: Atrasentan, ABT-627, Baboon, Endothelin, PET