A novel 99mTc-labeled molecular probe for tumor angiogenesis imaging in hepatoma xenografts model: a pilot study.
A novel 99mTc-labeled molecular probe for tumor angiogenesis imaging in hepatoma xenografts model: a pilot study.
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用于肝癌异种移植模型肿瘤血管生成成像的新型 99mTc 标记分子探针：初步研究
DOI：
10.1371/journal.pone.0061043
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Yin L
中科院分区：
文献类型：
--
作者：
Zhao Q;Yan P;Wang RF;Zhang CL;Li L;Yin L
采用放射性核素靶向的肿瘤血管生成可视化提供了重要的诊断信息。在前期的研究中，我们证明了精氨酸-精氨酸-亮氨酸（RRL）肽段应该是肿瘤内皮细胞特异性结合序列。本研究的总体目的是评估99mTc标记的RRL是否可以用于恶性肿瘤的体内无创成像，并作为一种新的靶向肿瘤血管生成的分子探针。方法设计RRL多肽，用99mTc一步法放射合成。然后在体外表征放射性标记效率和放射化学纯度。将99 mTc-RRL静脉注射给荷HepG2异种移植物的BALB/c裸小鼠。定期进行生物分布和体内成像。还探讨了肿瘤大小与99mTc-RRL的%ID摄取之间的关系。结果99mTc-RRL在室温下30-60 min内标记效率达76.9% ± 4.5%（n = 6），纯化后放化纯度大于96%。 体外稳定性实验表明放射性标记的肽是稳定的。生物分布数据显示，99mTc-RRL从血液中迅速清除，并主要积聚在肾脏和肿瘤中。注射后肿瘤对99mTc-RRL的特异性摄取显著高于未标记RRL阻断和游离高锝酸对照试验（p <0.05）。肿瘤与肌肉的比值超过6.5，肿瘤与肝脏的比值达到1.98，肿瘤与血液的比值达到1.95。在平面γ显像研究中，注射99mTc-RRL后2-6h肿瘤显像清晰，而阻断组肿瘤显像不清晰。99mTc-RRL与18F-FDG PET显像的肿瘤/肌肉比值相当。免疫组化分析证实了肿瘤血管过多。肿瘤大小与99mTc-RRL摄取呈线性关系，R2 = 0.821。 结论99mTc-RRL可作为肿瘤血管生成显像的一种新方法。
Introduction Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether 99mTc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis. Methods The RRL peptide was designed and radiosynthesized with 99mTc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. 99mTc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of 99mTc-RRL was also explored. Results The labeling efficiencies of 99mTc-RRL reached 76.9%±4.5% (n = 6) within 30–60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that 99mTc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of 99mTc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2–6 h after injection of 99mTc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with 99mTc-RRL was comparable with that of 18F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of 99mTc-RRL with R2 = 0.821. Conclusion 99mTc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas.
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影响因子：
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作者：
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影响因子：
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