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

作者：Kawachi Emi; Uehara Yoshinari; Hasegawa Koki; Yahiro Eiji; Ando Setsuko; Wada Yasuhiro; Yano Tsuneo; Nishikawa Hiroaki; Shiomi Masashi; Miura Shin ichiro; Watanabe Yasuyoshi; Saku Keijiro^*

来源：Circulation Journal, 2013, 77(6): 1482-1489.

DOI：10.1253/circj.CJ-12-0736

• Apo A-I mimetic peptide
• Atherosclerosis
• High-density lipoprotein
• PET imaging
• Plaque

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, ape A-I (Milano) or full-length apo A-I is dramatically effective, it is still unclear whether apo A-I or ape 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. %26lt;br%26gt;Methods and Results: FAMP was modified with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and radiolabeled with gallium-68 (Ga-68) for noninvasive positron emission tomography (PET) in an animal model (familial hypercholesterolemic myocardial infarction-prone rabbits: WHHL-MI) with atherosclerotic lesions. The Ga-68-DOTA-FAMP was dramatically taken up by atherosclerotic tissues in the blood vessels and aorta of WHHL-Ml rabbits, but not the control rabbits. %26lt;br%26gt;Conclusions: An apo A-I mimetic peptide with Ga-68-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.

• 出版日期2013-6