Identification of Angiogenesis Rich-Viable Myocardium using RGD Dimer based SPECT after Myocardial Infarction

Cardiac healing after myocardial ischemia is a complex biological process. Advances in understanding of wound healing response have paved the way for clinical testing of novel molecular imaging to improve clinical outcomes. A key factor for assessing myocardial viability after ischemic injury is the evaluation of angiogenesis accompanying increased expression of integrin αvβ3. Here, we describe the capability of an αvβ3integrin-targeting SPECT agent,99mTc-IDA-D-[c(RGDfK)]2, for identification of ischemic but viable myocardium, i.e., hibernating myocardium which is crucial to predict functional recovery after revascularization, the standard care of cardiovascular medicine. In vivo SPECT imaging of rat models with transient coronary occlusion showed significantly high uptake of99mTc-IDA-D-[c(RGDfK)]2in the ischemic region. Comparative measurements with201Tl SPECT and18F-FDG PET, then, proved that such prominent uptake of99mTc-IDA-D-[c(RGDfK)]2exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of99mTc-IDA-D-[c(RGDfK)]2was non-inferior to that of18F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of99mTc-IDA-D-[c(RGDfK)]2corresponded to the vibrant angiogenic events with elevated expression of αvβ3integrin. Together, these results establish that99mTc-IDA-D-[c(RGDfK)]2SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization.