Cardiovascular molecular imaging is a rapidly evolving field of research, aiming to image and quantify molecular and cellular targets in vivo. Natriuretic peptides (NPs) can acts as a potent inhibitor of vascular smooth muscle cell migration and proliferation through activation of the clearance receptor (NPR-C). In this study, the potential use of a C-type NP fragment (C-ANF) to image the NPR-C receptor expression in developing plaque-like lesions in a rabbit atherosclerosis model and surgically ligated thigh of murine hindlimb ischemia model by functionalization with 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (DOTA) and labeled with copper-64 for non-invasive imaging with positron emission tomography (PET). Results clearly showed the significantly higher tracer uptake in the injured sites in both models compared to the contralateral control sites. PET imaging and competitive receptor blocking studies demonstrated the NPR-C receptor mediated tracer uptake.