title: SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides.
abstract: Vulnerable atherosclerotic plaques with unique biological signatures are responsible for most major cardiovascular events including acute myocardial infarction and stroke. However, current clinical diagnostic approaches for atherosclerosis focus on anatomical measurements such as the degree of luminal stenosis and wall thickness. An abundance of neovessels with elevated expression of integrin αvβ3 is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an αvβ3 integrin-targeting radiotracer, (99m)Tc-IDA-D-[c(RGDfK)]2, for SPECT/CT imaging of high-risk plaque in murine atherosclerosis models. In vivo uptake of (99m)Tc-IDA-D-[c(RGDfK)]2 was significantly higher in atherosclerotic aortas than in relatively normal aortas. Comparison with the negative-control peptide, (99m)Tc-IDA-D-[c(RADfK)]2, proved specific binding of (99m)Tc-IDA-D-[c(RGDfK)]2 for plaque lesions in in vivo SPECT/CT and ex vivo autoradiographic imaging. Histopathological characterization revealed that a prominent SPECT signal of (99m)Tc-IDA-D-[c(RGDfK)]2 corresponded to the presence of high-risk plaques with a large necrotic core, a thin fibrous cap, and vibrant neoangiogenic events. Notably, the RGD dimer based (99m)Tc-IDA-D-[c(RGDfK)]2 showed better imaging performance in comparison with the common monomeric RGD peptide probe (123)I-c(RGDyV) and fluorescence tissue assay corroborated this. Our preclinical data demonstrated that (99m)Tc-IDA-D-[c(RGDfK)]2 SPECT/CT is a sensitive tool to noninvasively gauge atherosclerosis beyond vascular anatomy by assessing culprit plaque neovascularization.
authors.affiliation: 1] Smart Humanity Convergence Center, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, Republic of Korea [2] Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270, Republic of Korea.
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Yoo
authors.affiliation: 1] Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung 210-701, Republic of Korea [2] Catholic Kwandong University International St. Mary's Hospital, Incheon 404-834, Republic of Korea.
authors.forename: Jonghwan
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Jung
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.affiliation: 1] Institute for Bio-Medical Convergence, College of Medicine, Catholic Kwandong University, Gangneung 210-701, Republic of Korea [2] Catholic Kwandong University International St. Mary's Hospital, Incheon 404-834, Republic of Korea.
authors.forename: Soonhag
authors.initials: S
authors.lastname: Kim
authors.affiliation: 1] Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea [2] Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270, Republic of Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.affiliation: 1] Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea [2] Smart Humanity Convergence Center, Program in Biomedical Radiation Sciences, Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Suwon 443-270, Republic of Korea [3] Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 443-270, Republic of Korea.
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000000981:diagnostic imaging*; D016023:Integrins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010456:Peptides, Cyclic / Q000493:pharmacokinetics*; D058226:Plaque, Atherosclerotic / Q000000981:diagnostic imaging*; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C000608779:99mTc-IDA-D-(c(RGDfK))2; D016023:Integrins; D015609:Organotechnetium Compounds; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals