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.
James R Hill  1  2 ,  Xia Shao  2 ,  Jay S Wright  2 ,  Jenelle Stauff  2 ,  Phillip S Sherman  2 ,  Janna Arteaga  2 ,  Ka Kit Wong  2 ,  Benjamin L Viglianti  2  3 ,  Peter J H Scott  2 ,  Allen F Brooks  2
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.
PMID: 32551015 DOI: 10.1021/acsmedchemlett.0c00127
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.

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