SPECT/CT Imaging of High-Risk Atherosclerotic Plaques using Integrin-Binding RGD Dimer Peptides

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 lumin...

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Veröffentlicht in:Scientific reports 2015-06, Vol.5 (1), p.11752, Article 11752
Hauptverfasser: Sun Yoo, Jung, Lee, Jonghwan, Ho Jung, Jae, Seok Moon, Byung, Kim, Soonhag, Chul Lee, Byung, Eun Kim, Sang
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Sprache:eng
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Zusammenfassung: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 α v β 3 is closely associated with an increased risk of plaque rupture. Herein we evaluated the potential of an α v β 3 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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep11752