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In vivo Near Infrared Fluorescence (NIRF) Intravascular Molecular Imaging of Inflammatory Plaque, a Multimodal Approach to Imaging of Atherosclerosis
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Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V: a technique with potential

Frank D Kolodgie1, Artiom Petrov, Renu Virmani

  • 1Armed Forces Institute of Pathology, Washington, DC, USA.

Circulation
|December 17, 2003
PubMed
Summary

Radiolabeled annexin V effectively detects apoptosis in atherosclerotic plaques. This imaging agent targets macrophages, aiding in the noninvasive identification of unstable plaques.

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Area of Science:

  • Cardiovascular Research
  • Molecular Imaging
  • Pathology

Background:

  • Apoptosis is prevalent in advanced human atheroma, contributing to plaque instability.
  • Annexin V binds to phosphatidylserine on apoptotic cells, enabling noninvasive detection of apoptosis in atherosclerotic lesions.

Purpose of the Study:

  • To evaluate the utility of radiolabeled annexin V as a noninvasive imaging agent for detecting apoptosis in atherosclerotic plaques.

Main Methods:

  • Atherosclerotic plaques were induced in rabbits via deendothelialization and cholesterol diet.
  • Animals received technetium-99m-labeled human recombinant annexin V, followed by in vivo and ex vivo imaging.
  • Histological analysis, including DNA fragmentation staining and macrophage burden assessment, was performed.

Main Results:

  • Rapid clearance of radiolabeled annexin V from circulation (T1/2, alpha 9 and beta 46 minutes).
  • Intense radiolabel uptake in atherosclerotic lesions within 2 hours, confirmed ex vivo; no uptake in controls.
  • Annexin V uptake correlated with lesion severity, macrophage burden, and apoptotic index, but not smooth muscle cells.

Conclusions:

  • Rapid blood clearance and targeted uptake by apoptotic macrophages make annexin V a promising imaging agent.
  • Annexin V facilitates noninvasive detection of unstable atherosclerotic plaques.