Novel Molecular Imaging of Atherosclerosis With Gallium-68-Labeled Apolipoprotein A-I Mimetic Peptide and Positron Emission Tomography

  • Kawachi Emi
    Department of Cardiology, Fukuoka University School of Medicine
  • Uehara Yoshinari
    Department of Cardiology, Fukuoka University School of Medicine
  • Hasegawa Koki
    RIKEN Center for Molecular Imaging Science
  • Yahiro Eiji
    Department of Cardiology, Fukuoka University School of Medicine Department of Community and Emergency Medicine, Fukuoka University
  • Ando Setsuko
    Department of Chemistry, Faculty of Science, Fukuoka University
  • Wada Yasuhiro
    RIKEN Center for Molecular Imaging Science
  • Yano Tsuneo
    RIKEN Center for Molecular Imaging Science
  • Nishikawa Hiroaki
    Department of Cardiology, Fukuoka University School of Medicine
  • Shiomi Masashi
    Institute for Experimental Animals, Kobe University Graduate School of Medicine
  • Miura Shin-ichiro
    Department of Cardiology, Fukuoka University School of Medicine
  • Watanabe Yasuyoshi
    RIKEN Center for Molecular Imaging Science
  • Saku Keijiro
    Department of Cardiology, Fukuoka University School of Medicine

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Other Title
  • Novel molecular imaging of atherosclerosis with 68Ga-labeled apo A-I mimetic peptide and positron emission tomography

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Abstract

Background: High-density lipoprotein (HDL) plays a major role in reverse cholesterol transport. Many researchers have been working to enhance the biochemical function of HDL for use in therapy. Although HDL therapy using injections of apolipoprotein (apo)-A-I mimetics, apo A-I Milano or full-length apo A-I is dramatically effective, it is still unclear whether apo A-I or apo A-I mimetics actually enter atherosclerotic plaque and remove cholesterol from the lipid burden. We synthesized a novel 24-amino acid apo A-I mimetic peptide (known as FAMP) that potently removes cholesterol via specific ATP-binding cassette transporter A1. We then investigated the potential of FAMP to image developing plaque lesions in vivo. Methods and Results: FAMP was modified with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with gallium-68 (68Ga) for noninvasive positron emission tomography (PET) in an animal model (familial hypercholesterolemic myocardial infarction-prone rabbits: WHHL-MI) with atherosclerotic lesions. The 68Ga-DOTA-FAMP was dramatically taken up by atherosclerotic tissues in the blood vessels and aorta of WHHL-MI rabbits, but not the control rabbits. Conclusions: An apo A-I mimetic peptide with 68Ga-DOTA is a promising candidate diagnostic tracer for PET imaging of the atherosclerotic lipid burden and may contribute to the development of a tool for the diagnosis of plaque with PET.  (Circ J 2013; 77: 1482–1489)<br>

Journal

  • Circulation Journal

    Circulation Journal 77 (6), 1482-1489, 2013

    The Japanese Circulation Society

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