Use of radioiodinated peptide Arg-Arg-Leu targeted to neovascularization as well as tumor cells in molecular tumor imaging
Use of radioiodinated peptide Arg-Arg-Leu targeted to neovascularization as well as tumor cells in molecular tumor imaging
复制标题
在分子肿瘤成像中使用放射性碘标记的肽 Arg-Arg-Leu 靶向新血管形成以及肿瘤细胞
DOI：
10.1007/s11670-012-0052-8
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发表时间：
2012-03-01
影响因子：
5.1
通讯作者：
Zhang, Chun-li
中科院分区：
文献类型：
--
作者：
Lu, Xia;Yan, Ping;Zhang, Chun-li
目的探索一种靶向肿瘤细胞和肿瘤内皮细胞的肿瘤多肽显像剂精氨酸-精氨酸-亮氨酸-亮氨酸(Tyr-Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys，TRRL)，初步探讨TRRL与血管内皮生长因子受体2(VEGFR-2)的关系。将酪氨酸偶联到RRL(Cys-Gly-Gly-Arg-Arg-Leu-Gly-Cys)的氨基末端，用于放射性核素~(131)I标记。用流式细胞仪和放射性计数器研究TRRL对肿瘤细胞和血管内皮细胞的摄取能力和分子结合能力。研究了VEGFR-2是否是TRRL的结合部位。通过~(131)I-TRRL的生物分布和单光子发射计算机断层扫描(SPECT)成像来评价这种新型显像剂在裸鼠体内对各种肿瘤移植瘤的显示效果。结果体外细胞摄取实验表明，TRRL不仅能与肿瘤血管生成的内皮细胞黏附，而且能在恶性肿瘤细胞内大量蓄积。VEGFR-2在TDEC上高表达，可能不是TRRL靶向肿瘤血管内皮细胞的唯一结合配体。131I-TRRL注射后24小时主要蓄积在肿瘤体内，而不是其他器官。~(131)I-TRRL SPECT显像能清晰显示裸鼠体内的肿瘤，尤其是在24小时。结论放射性核素标记的TRRL为肿瘤新生血管的功能分子成像提供了一种无创的核成像方法，有望成为肿瘤放射免疫治疗的载体。
ObjectiveTo explore a tumor peptide imaging agent Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys, tripeptide RRL [tRRL]) that targeted to tumor cells and tumor-derived endothelial cells (TDECs) and primarily investigate the possible relationship between tRRL and vascular endothelial growth factor receptor 2 (VEGFR-2).MethodsThe tRRL sequence motif was identified as a tumor molecular marker specifically binding to TDECs. Tyrosine was conjugated to the amino terminal of RRL (Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys) for labeling with radionuclide iodine-131 (131I-tRRL). The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counterin vitro. Whether VEGFR-2 is the binging site of tRRL was investigated. Biodistribution and single-photon emission computed tomography (SPECT) imaging of131I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice.ResultsIn vitrocellular uptake experiments revealed that tRRL could not only adhere to tumor angiogenic endothelial cells but also largely accumulate in malignant tumor cells. VEGFR-2, which is highly expressed on TDECs, was probably not the solely binding ligand for tRRL targeted to tumor angiogenic endothelium.131I-tRRL mainly accumulated in tumorsin vivo, not other organs at 24 h after injection. SPECT imaging with131I-tRRL clearly visualized tumors in nude mice, especially at 24 h.ConclusionRadioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors targeted to neovascularization, and may be a promising candidate for tumor radioimmunotherapeutic carrier.