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 αvβ3 integrin-targeting SPECT agent, (99m)Tc-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 of (99m)Tc-IDA-D-[c(RGDfK)]2 in the ischemic region. Comparative measurements with (201)Tl SPECT and (18)F-FDG PET, then, proved that such prominent uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 exactly matched the hallmark of hibernation, i.e., the perfusion-metabolism mismatch pattern. The uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was non-inferior to that of (18)F-FDG, confirmed by time-course variation analysis. Immunohistochemical characterization revealed that an intense signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the vibrant angiogenic events with elevated expression of αvβ3 integrin. Together, these results establish that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT can serve as a sensitive clinical measure for myocardial salvage to identify the patients who might benefit most from revascularization.
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Smart Humanity Convergence Center, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Min Su
MS
Lee
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Smart Humanity Convergence Center, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Hyun Soo
HS
Park
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon, Republic of Korea.
Byung Chul
BC
Lee
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jae Ho
JH
Jung
Smart Humanity Convergence Center, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.|Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon, Republic of Korea.
Jung Sun
JS
Yoo
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.|Smart Humanity Convergence Center, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.|Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon, Republic of Korea.
Sang Eun
SE
Kim
D000818:Animals; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D015609:Organotechnetium Compounds / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C047981:arginyl-glycyl-aspartic acid