新型动脉粥样硬化斑块示踪剂68Ga-NOTA-CD44的制备与生物学评价
Synthesis and biological evaluation of 68Ga-NOTA-CD44:a novel tracer targeting atherosclerotic plaques
王波 1李莉 1宇雪 2张楚欣 1鄢敏 1李慧玲 1茹慧宾 1武萍 1王若楠 1武志芳 1李思进1
作者信息
- 1. 山西医科大学第一医院核医学科、分子影像精准诊疗省部共建协同创新中心,太原 030001
- 2. 山西医科大学医学影像学院,太原 030001
- 折叠
摘要
目的 构建靶向透明质酸(HA)新型动脉粥样硬化(AS)示踪剂68Ga-1,4,7-三氮杂环壬烷-1,4,7-三乙酸(NOTA)-CD44,并进行生物学评价及分子显像研究.方法 选取小分子人重组CD44蛋白,在该蛋白羧基末端(C端)通过磺基化修饰后偶联双功能配体NOTA,合成靶向HA的核素标记分子探针68Ga-NOTA-CD44.研究探针的标记率、体外稳定性等生物学性质,并对3只AS斑块模型小鼠及3只正常C57BL/6小鼠行68Ga-NOTA-CD44 microPET/CT显像及病理对照研究.结果 合成的探针68Ga-NOTA-CD44放化纯大于99％,比活度为62.22 MBq/nmol;探针在PBS中稳定性良好,放置3 h放化纯大于90％;探针经静脉注射后主要经肾代谢,在肝、肺及血液中代谢依次减低.AS模型小鼠microPET/CT显像示,该探针注射后60 min腹主动脉斑块处摄取较高,SUVmax与靶/本底比(TBR)max分别为1.14±0.02及4.95±0.93,具有一定的AS侵蚀斑块靶向性,与病理结果一致.结论 新型分子探针68Ga-NOTA-CD44的制备简便且标记率高,具有较好的理化性质及体内生物学性质,靶向显示AS侵蚀斑块的灵敏度高,其分子影像在早期无创识别AS侵蚀斑块方面具有良好应用前景.
Abstract
Objective To construct 68Ga-1,4,7-trizacyclononane-1,4,7-triacetic acid(NOTA)-CD44 as a novel atherosclerosis tracer targeting hyaluronic acid(HA),and evaluate its biological property and molecular imaging features.Methods Low molecular weight(LMW)recombinant human CD44 pro-tein was selected,and the C-terminal of the protein was modified by sulfonation and coupled to the bifunc-tional ligand NOTA to synthesize a novel molecular probe 68Ga-NOTA-CD44 targeting HA.The biological properties of the probe,such as labeling rate and in vitro stability,were studied.Three atherosclerotic plaque model mice and three normal C57BL/6 mice were studied by 68Ga-NOTA-CD44 microPET/CT ima-ging and pathological examination.Results 68Ga-NOTA-CD44 tracer was synthesized and purified with the radiochemical purity above 99％,and the specific activity was up to 62.22 MBq/nmol.Its stability was good in PBS,and the radiochemical purity was over 90％after incubation for 3 h.After intravenous injection,the probe was metabolized mainly by the kidneys,and its metabolic level decreased successively in the liver,lungs and blood.MicroPET/CT imaging results of atherosclerotic model mice suggested that the uptake in the plaque of abdominal aorta was higher at 60 min after injection,with SUVmax and target/background ratio(TBR)max of 1.14±0.02 and 4.95±0.93,and the probe had certain atherosclerotic plaque eroded targeting,which was consistent with the pathological result.Conclusions As a novel probe,68Ga-NOTA-CD44 is simple to prepare and has a high labeling rate.It has good physicochemical properties and in vivo biological properties,and can display atherosclerotic eroded plaques sensitively.68Ga-NOTA-CD44 has a promising prospect to be a new molecular probe for early noninvasive recognition of atherosclerotic eroded plaques.
关键词
斑块,动脉粥样硬化/抗原,CD44/同位素标记/镓放射性同位素/小鼠Key words
Plaque,atherosclerotic/Antigens,CD44/Isotope labeling/Gallium radioisotopes/Mice引用本文复制引用
出版年
2024
NETL
NSTL
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