biostudies-literatureSultan DBLRD VANHLBIFoundation for Barnes-Jewish HospitalCystic Fibrosis FoundationNIAID NIH HHSNHLBI NIH HHSNational Institutes of HealthNIAIDU.S. Department of Veterans AffairsVeterans Health Administration Biomedical Laboratory Research and Development102416https://www.ebi.ac.uk/biostudies/studies/S-EPMC8684599biostudies-literatureUnknown36The 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.Nanomedicine : nanotechnology, biology, and medicineAssessment of ultrasmall nanocluster for early and accurate detection of atherosclerosis using positron emission tomography/computed tomography.PMC8684599R01HL153436R01HL094601I01 BX002730R01HL151078R01 HL151078P01 AI116501R01 HL153436R01 HL094601R35 HL1452121I01BX002730Li WLiu YHeo GSLuehmann HPKreisel DSultan DDetering LfalseAssessment of ultrasmall nanocluster for early and accurate detection of atherosclerosis using positron emission tomography/computed tomography.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.2021-01-01T00:00:00Z2021 Aug2025-04-05T16:11:29.436Z2025-04-05T16:11:29.436ZS-EPMC86845993414766210.1016/j.nano.2021.102416