Molecular Imaging of Vulnerable Plaque

Many cellular and molecular pathways are involved in the pathogenesis of vulnerable plaque. The developing role of new nuclear medicine imaging techniques surpassed the conventional morphological evaluation, permitting the assessment of specific bio-molecular targets involved in the plaque pathogenesis. The most widely diffuse tracer in PET imaging is 18FDG. 18FDG-PET has the potential to diagnose and monitor the inflammatory activity of macrophages within the atherosclerotic plaque and could serve for the prognostic evaluation of these lesions. Further PET imaging applications have been evaluated for precise assessment of the CXCR4-expressing plaque burden of the vessel wall that may allow for more reliable identification of patients that would most likely benefit from innovative CXCR4-targeting therapies. In this setting, 68Ga-Pentixafor PET/CT identified a broad spectrum of coronary plaques, including stented culprit, stented non-culprit, non-stented non-culprit coronary lesions. Another clinical prominent characteristic of atherosclerosis is the presence of calcium deposition that may be also assessed using NaF PET. The tracer uptake of NaF has been demonstrated to be microscopically correlated with calcification (instead of inflammation) and potentially useful in risk’s stratification of patients. Recent research has focused on the development of smart imaging radiotracers targeting specific agents/biomarkers as favorable targets for in vivo assessment of angiogenesis. Nuclear medicine advancements have been proposed in preparations of 18F-labeled, 64Cu-labeled, and 68Ga-labeled RGD PET tracers, for imaging receptor integrin αvß3 expression but the translation in clinical practice is still limited. Another particular target of the atherosclerosis is the macrophagic activation in atherosclerosis process and the somatostatin receptor expression. The subtype 2 of somatostatin receptor has been shown to be upregulated on the surface of pro-inflammatory M1 macrophages. SSRT-2 receptor PET imaging, able to target activated inflammatory cells, appears to be a possible valuable alternative to 18F-FDG PET/CT, opening a possible future scenario for theranostic application.