Translocator Protein Ligand Has Improved Binding Characteristics For Quantification of Macrophages in Atherosclerosis

Carotid atherosclerotic plaque rupture is clinically assessed by vessel stenosis. High macrophage content is a consistent finding in ruptured plaques and the translocator protein (TSPO) is highly expressed in activated macrophages. TSPO ligands exist which are readily labelled by positron emission tomography (PET) radionuclides and thus, may non-invasively quantify macrophage burden. However, many of these have high non-specific binding (NSB) producing disparity between total and specific binding. Since total binding is the measure obtained in a clinical setting, reduction in NSB will improve macrophage quantification. We have previously shown that other TSPO ligands bind with high affinity to macrophages and binding correlates with macrophages in atherosclerotic plaque. However, NSB is typically greater than 50% of total binding on rabbit and human tissues. N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7 …