Cardiovascular Center, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
Nuclear Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, South Korea.
J Nucl Med. 2016 Nov;57(11):1792-1797. doi: 10.2967/jnumed.116.172650. Epub 2016 Jun 23.
Activated macrophages take up F-FDG via glucose transporters, so this compound is useful for atherosclerosis imaging by PET. However, F-FDG application is limited for imaging of the heart and brain, in which glucose uptake is high, and in patients with aberrant glucose metabolism. The aims of this study were to confirm that mannosylated human serum albumin (MSA) specifically binds to the mannose receptor (MR) on macrophages and to test the feasibility of Ga-labeled NOTA-MSA for PET imaging of atherosclerotic plaques.
The peritoneal macrophages of C57/B6 mice were collected, incubated with rhodamine B isothiocyanate-MSA (10 μg/mL), and evaluated by confocal microscopy and flow cytometry. The same evaluations were performed after preincubation of the macrophages with anti-CD206 MR blocking antibodies. NOTA-MSA was synthesized by conjugating 2-(p-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid to MSA, followed by labeling with Ga. Rabbits with atherosclerotic aorta induced by a 3-mo cholesterol diet and chronic inflammation underwent consecutive PET/CT with F-FDG and Ga-NOTA-MSA at 2-d intervals.
The binding of MSA to MR and its dose-dependent reduction by preincubation with anti-CD206 MR blocking antibody were confirmed. Rhodamine B isothiocyanate and fluorescein isothiocyanate fluorescence colocalized at the atherosclerotic plaque. The Ga-NOTA-MSA SUVs of the atherosclerotic aorta were significantly higher than those of the healthy arteries and inferior vena cava and were comparable to those obtained with F-FDG.
These findings suggest that MR-specific Ga-NOTA-MSA is effective for detecting atherosclerosis in the aorta and is a promising radiopharmaceutical for imaging atherosclerosis because of the presence of M2 macrophages in atherosclerotic plaques.
通过葡萄糖转运蛋白，活化的巨噬细胞摄取 F-FDG，因此这种化合物可用于 PET 对动脉粥样硬化的成像。然而，由于心脏和大脑中葡萄糖摄取量高，以及葡萄糖代谢异常的患者，F-FDG 的应用受到限制。本研究的目的是证实甘露糖化人血清白蛋白（MSA）特异性结合到巨噬细胞上的甘露糖受体（MR），并测试 Ga 标记的 NOTA-MSA 用于动脉粥样硬化斑块的 PET 成像的可行性。
收集 C57/B6 小鼠的腹腔巨噬细胞，用 rhodamine B 异硫氰酸酯-MSA（10 μg/mL）孵育，并通过共聚焦显微镜和流式细胞术进行评估。在用抗 CD206 MR 阻断抗体预孵育巨噬细胞后，进行相同的评估。通过将 2-（对异硫氰酸苯甲基）-1,4,7-三氮杂环壬烷-1,4,7-三乙酸偶联到 MSA 上，然后用 Ga 标记来合成 NOTA-MSA。通过 3 个月的胆固醇饮食和慢性炎症诱导动脉粥样硬化的兔，在 2 天的间隔内连续进行 F-FDG 和 Ga-NOTA-MSA 的 PET/CT。
证实了 MSA 与 MR 的结合及其与抗 CD206 MR 阻断抗体预孵育的剂量依赖性减少。异硫氰酸罗丹明 B 和异硫氰酸荧光素荧光在动脉粥样硬化斑块处共定位。动脉粥样硬化主动脉的 Ga-NOTA-MSA SUV 明显高于健康动脉和下腔静脉，与 F-FDG 获得的 SUV 相当。
这些发现表明，MR 特异性 Ga-NOTA-MSA 可有效检测主动脉中的动脉粥样硬化，并且由于动脉粥样硬化斑块中存在 M2 巨噬细胞，因此是一种很有前途的用于动脉粥样硬化成像的放射性药物。
