Open AccessSynthesis and Evaluation of 11C- and 18F-Labeled SOAT1 Inhibitors as Macrophage Foam Cell Imaging Agents
Author(s) -
J. R. Hill,
Xia Shao,
Jay Wright,
Jenelle Stauff,
Phillip Sherman,
Janna Arteaga,
Ka Kit Wong,
Benjamin L. Viglianti,
Peter J. H. Scott,
Allen F. Brooks
Publication year - 2020
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.0c00127
Subject(s) - biodistribution , sterol o acyltransferase , medicine , positron emission tomography , pharmacology , endocrinology , chemistry , cholesterol , nuclear medicine , biochemistry , lipoprotein , in vitro
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.