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

Jung Sun Yoo1, Jonghwan Lee2, Jae Ho Jung3

  • 11] 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.

Scientific Reports
|July 1, 2015
PubMed

Insights

A new radiotracer, (99m)Tc-IDA-D-[c(RGDfK)]2, effectively images high-risk atherosclerotic plaques by targeting integrin αvβ3. This imaging tool assesses plaque neovascularization, offering a new way to diagnose vulnerable plaques beyond anatomical measurements.

Area of Science:

  • Cardiovascular Research
  • Molecular Imaging
  • Radiochemistry

Background:

  • Vulnerable atherosclerotic plaques are a primary cause of cardiovascular events like heart attack and stroke.
  • Current diagnostic methods for atherosclerosis primarily rely on anatomical assessments, such as luminal stenosis and wall thickness.
  • Neovessels within plaques, expressing integrin αvβ3, are linked to increased plaque rupture risk.

Purpose of the Study:

  • To evaluate the potential of a novel integrin αvβ3-targeting radiotracer, (99m)Tc-IDA-D-[c(RGDfK)]2, for SPECT/CT imaging of high-risk atherosclerotic plaques.
  • To assess the specificity and sensitivity of this radiotracer in preclinical atherosclerosis models.
  • To compare the imaging performance of the RGD dimer-based tracer with existing probes.

Main Methods:

  • Development and evaluation of the (99m)Tc-IDA-D-[c(RGDfK)]2 radiotracer.
  • In vivo SPECT/CT imaging in murine atherosclerosis models.
  • Comparison with a negative-control peptide, (99m)Tc-IDA-D-[c(RADfK)]2.
  • Ex vivo autoradiography and histopathological analysis of atherosclerotic plaques.
  • Comparison with a monomeric RGD peptide probe, (123)I-c(RGDyV).

Main Results:

  • The (99m)Tc-IDA-D-[c(RGDfK)]2 tracer showed significantly higher uptake in atherosclerotic aortas compared to normal aortas.
  • Specific binding of the tracer to plaque lesions was confirmed through in vivo and ex vivo imaging.
  • SPECT signals correlated with histopathological features of high-risk plaques, including large necrotic cores, thin fibrous caps, and neovascularization.
  • (99m)Tc-IDA-D-[c(RGDfK)]2 demonstrated superior imaging performance compared to the monomeric RGD peptide probe.

Conclusions:

  • The (99m)Tc-IDA-D-[c(RGDfK)]2 radiotracer is a sensitive tool for noninvasively imaging high-risk atherosclerotic plaques.
  • SPECT/CT imaging with this tracer can assess plaque neovascularization, providing biological insights beyond anatomical measurements.
  • This approach holds promise for improved diagnosis and risk stratification of atherosclerosis.