Targeting cardiovascular inflammation for imaging: Comparison of the uptake of multiple tracers in leukocyte subpopulations

Objectives: Localized inflammation in myocardium and vasculature has emerged as a therapeutic and imaging target for cardiovascular disease. A range of different radiotracers have been evaluated for assessment of inflammatory cell infiltration, but the precise cell populations responsible for the in vivo signal remain elusive. We aimed to characterize the cellular binding profiles of five candidate inflammation radiotracers. Methods: Radiotracers evaluated were: 18F-deoxyglucose (FDG), labeled amino acids 18F-fluoroethyltyrosine (FET) and 11C-methionine (MET), mitochondrial translocator protein (TSPO)-targeted 18F-GE180, and leukocyte-expressed chemokine receptor type 4 (CXCR4) targeted 68Ga-pentixafor. All tracers were previously shown to be useful for imaging of myocardial inflammation in preclinical and/or clinical models. Uptake assays were performed in THP-1 derived macrophages with classical polarization, and in peripheral blood leukocyte subpopulations purified by magnetic immunoseparation. Results: All tracers demonstrated specific uptake by polarized macrophages. FDG uptake was consistently higher than for other tracers, with intermediate uptake of GE180, and comparatively low accumulation of MET, FET, and pentixafor, reflecting slower transport rates of amino acids and lower expression of CXCR4, respectively. Most tracers showed higher accumulation in proinflammatory M1 macrophages over M2. FDG uptake was 20-fold higher in M1 compared to M2 (p