Novel molecular imaging of atherosclerosis with gallium-68-labeled apolipoprotein A-I mimetic peptide and positron emission tomography.
Novel molecular imaging of atherosclerosis with gallium-68-labeled apolipoprotein A-I mimetic peptide and positron emission tomography.
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DOI：
10.1253/circj.cj-12-0736
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发表时间：
2013-05
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通讯作者：
Emi Kawachi;Y. Uehara;K. Hasegawa;E. Yahiro;S. Ando;Yasuhiro Wada;T. Yano;H. Nishikawa;M. Shiomi;S. Miura;Yasuyoshi Watanabe;K. Saku
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文献类型：
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作者：
Emi Kawachi;Y. Uehara;K. Hasegawa;E. Yahiro;S. Ando;Yasuhiro Wada;T. Yano;H. Nishikawa;M. Shiomi;S. Miura;Yasuyoshi Watanabe;K. Saku
背景高密度脂蛋白(HDLc)在胆固醇逆向转运中起重要作用。许多研究人员一直致力于增强高密度脂蛋白的生化功能，以用于治疗。尽管注射载脂蛋白(Apo)-A-I模拟物、apo A-I Milano或全长apo A-I的高密度脂蛋白治疗非常有效，但仍不清楚apo A-I或apo A-I模拟物是否真的进入动脉粥样硬化斑块并从脂质负担中去除胆固醇。我们合成了一种新的24个氨基酸的载脂蛋白A-I模拟肽(FAMP)，它通过特异的ATP结合盒转运蛋白A1有效地清除胆固醇。然后，我们研究了FAMP在体内成像正在形成的斑块病变的可能性。方法和结果在动脉粥样硬化病变的家族性高胆固醇血症心肌梗死动物模型(家族性高胆固醇血症心肌梗死家兔：1，4，7，10-tetraazacyclododecane-1，4，7，10-tetraacetic-MI)上，用DOTA修饰FAMP并用~(68)Ga标记FAMP进行正电子发射断层扫描。(68)Ga-DOTA-FAMP在WHHL-MI兔的血管和主动脉中被动脉粥样硬化组织显著摄取，而对照兔则不被摄取。结论含(68)Ga-DOTA的apo A-I模拟多肽是一种很有前途的诊断示踪剂，可用于动脉粥样硬化性脂质负荷的PET成像，并可能有助于开发一种PET诊断斑块的工具。
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 ((68)Ga) for noninvasive positron emission tomography (PET) in an animal model (familial hypercholesterolemic myocardial infarction-prone rabbits: WHHL-MI) with atherosclerotic lesions. The (68)Ga-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 (68)Ga-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.