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

James R Hill; Xia Shao; Jay S Wright; Jenelle Stauff; Phillip S Sherman; Janna Arteaga; Ka Kit Wong; Benjamin L Viglianti; Peter J H Scott; Allen F Brooks

doi:10.1021/acsmedchemlett.0c00127

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

ACS Med Chem Lett. 2020 Apr 30;11(6):1299-1304. doi: 10.1021/acsmedchemlett.0c00127. eCollection 2020 Jun 11.

Authors

Affiliations

¹ Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
² Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109, United States.
³ Nuclear Medicine Service, Veterans Administration, Ann Arbor, Michigan 48105, United States.

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, [¹¹C]PD-132301 and fluorine analogue [¹⁸F]1. Rat biodistribution studies were conducted with both agents and, as the most selective tracer, [¹¹C]PD-132301 was advanced to preclinical positron emission tomography studies in (atherosclerotic) ApoE^-/- mice. The uptake of [¹¹C]PD-132301 in SOAT1-rich tissue warrants further investigation into the compound as an atherosclerosis and adrenal imaging agent.