Work

Synthesis and Evaluation of 11C- and 18F-Labeled SOAT1 Inhibitors as Macrophage Foam Cell Imaging Agents

Year: 2020

Type: article

Abstract: PD-132301, an inhibitor of sterol O -acyltransferase 1 (SOAT1; also known as acyl-coenzyme A:cholesterol acyltransferase-1, ACAT1), is under clinical investigation for numerous adrenal disorders. Radiolabeled SOAT1 inhibitors could support drug discovery and help diagnose SOAT1-related disorders, such as atherosclerosis. We synthesized two radiolabeled SOAT1 inhibitors, [ 11 C]PD-132301 and fluorine analogue [ 18 F] 1 . Rat biodistribution studies were conducted with both agents and, as the most selective tracer, [ 11 C]PD-132301 was advanced to preclinical positron emission tomography studies in (atherosclerotic) ApoE –/– mice. The uptake of [ 11 C]PD-132301 in SOAT1-rich tissue warrants further investigation into the compound as an atherosclerosis and adrenal imaging agent.

Source: ACS Medicinal Chemistry Letters

DOI: 10.1021/acsmedchemlett.0c00127