Izawa Michi, Kawashima Hidekazu, Okuno Yui, Nakaya Junna, Takeda Mayuko, Harada Koki, Yamada Yuri, Nishimura Kaneyasu, Ishihara Keiichi, Akiba Satoshi, Takata Kazuyuki
Joint Research Laboratory, Division of Integrated Pharmaceutical Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto, 607-8414, Japan.
Radioisotope Research Center, Division of Integrated Pharmaceutical Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina-Ku, Kyoto, 607-8414, Japan.
Mol Imaging Biol. 2024 Dec;26(6):903-911. doi: 10.1007/s11307-024-01951-9. Epub 2024 Sep 17.
Bioimaging such as magnetic resonance is used to monitor atherosclerotic plaques consisting of foam cells, which are derived from macrophages that have ingested oxidized low-density lipoprotein (oxLDL). However, the current bioimaging techniques are not highly specific and sensitive in detecting foam cells, calling for the development of higher precision foam cell detection probes. Here, we investigated the utility of iodine-125-labeled oxLDL (I-oxLDL) as a prototype radiotracer in the radioimaging of foam cells infiltrating atherosclerotic plaques. Mouse bone marrow-derived macrophages (BMDMs) were used to analyze oxLDL uptake. Atherosclerosis mouse model was injected with I-oxLDL and DiI-labeled oxLDL (DiI-oxLDL). Accumulation of I-oxLDL and DiI-oxLDL in foam cells infiltrating atherosclerotic plaques was examined using Oil Red O (ORO) staining, autoradiography, and fluorescent immunohistochemistry. BMDMs phagocytosed oxLDL/I-oxLDL via CD36, but not LDL/I-LDL. The radioactive signal from I-oxLDL phagocytosed by the BMDMs could be detected for at least 3 days. In atherosclerosis mouse model, atherosclerotic plaques formed in the aortic arches and valves. The radioactive signal of the injected I-oxLDL was detected in atherosclerotic plaques of the aortic arch, and its intensity was positively correlated with the lesion size. Furthermore, the DiI-oxLDL fluorescent signals were detected in foam cells accumulating in atherosclerotic plaques. Thus, we found that I-oxLDL can be used as a radiotracer in the radioimaging of foam cells in atherosclerotic plaques by autoradiography, suggesting its potential future applications in bioimaging methods such as single-photon emission computed tomography.
诸如磁共振成像等生物成像技术被用于监测由泡沫细胞组成的动脉粥样硬化斑块，这些泡沫细胞源自摄取了氧化型低密度脂蛋白（oxLDL）的巨噬细胞。然而，当前的生物成像技术在检测泡沫细胞方面并非高度特异和灵敏，因此需要开发更高精度的泡沫细胞检测探针。在此，我们研究了碘-125标记的oxLDL（I-oxLDL）作为一种原型放射性示踪剂在浸润动脉粥样硬化斑块的泡沫细胞放射性成像中的效用。使用小鼠骨髓来源的巨噬细胞（BMDMs）来分析oxLDL的摄取情况。给动脉粥样硬化小鼠模型注射I-oxLDL和碘化油（DiI）标记的oxLDL（DiI-oxLDL）。使用油红O（ORO）染色、放射自显影和荧光免疫组织化学检查I-oxLDL和DiI-oxLDL在浸润动脉粥样硬化斑块的泡沫细胞中的积累情况。BMDMs通过CD36吞噬oxLDL/I-oxLDL，但不吞噬LDL/I-LDL。BMDMs吞噬的I-oxLDL的放射性信号至少可以检测3天。在动脉粥样硬化小鼠模型中，主动脉弓和瓣膜处形成了动脉粥样硬化斑块。在主动脉弓的动脉粥样硬化斑块中检测到了注射的I-oxLDL的放射性信号，其强度与病变大小呈正相关。此外，在积聚于动脉粥样硬化斑块中的泡沫细胞中检测到了DiI-oxLDL荧光信号。因此，我们发现I-oxLDL可通过放射自显影用作动脉粥样硬化斑块中泡沫细胞放射性成像的放射性示踪剂，这表明其在诸如单光子发射计算机断层扫描等生物成像方法中具有潜在的未来应用价值。
