Assessment of ultrasmall nanocluster for early and accurate detection of atherosclerosis using positron emission tomography/computed tomography.

ABSTRACT

The development of atherosclerosis therapy is hampered by the lack of molecular imaging tools to identify the relevant biomarkers and determine the dynamic variation in vivo. Here, we show that a chemokine receptor 2 (CCR2) targeted gold nanocluster conjugated with extracellular loop 1 inverso peptide (AuNC-ECL1i) determines the initiation, progression and regression of atherosclerosis in apolipoprotein E knock-out (ApoE-/-) mouse models. The CCR2 targeted 64Cu-AuNC-ECL1i reveals sensitive detection of early atherosclerotic lesions and progression of plaques in ApoE-/- mice. CCR2 targeting specificity was confirmed by the competitive receptor blocking studies. In a mouse model of aortic arch transplantation, 64Cu-AuNC-ECL1i accurately detects the regression of plaques. Human atherosclerotic tissues show high expression of CCR2 related to the status of the disease. This study confirms CCR2 as a useful marker for atherosclerosis and points to the potential of 64Cu-AuNC-ECL1i as a targeted molecular imaging probe for future clinical translation.