2. Academic Validation
  3. Synthesis and Evaluation of 11C- and 18F-Labeled SOAT1 Inhibitors as Macrophage Foam Cell Imaging Agents

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

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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