Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China ; Radiology Center, Beijing Aerospace General Hospital, Beijing 100076, China ; Key Laboratory of Radiopharmaceuticals (Ministry of Education), College of Chemistry, Beijing Normal University, Beijing 100191, China.
Chin J Cancer Res. 2012 Mar;24(1):52-9. doi: 10.1007/s11670-012-0052-8.
To 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).
The 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 ((131)I-tRRL). The uptake ability and molecular binding of tRRL to tumor cells and angiogenic endothelium were studied using flow cytometry and radioactivity counter in vitro. Whether VEGFR-2 is the binging site of tRRL was investigated. Biodistribution and single-photon emission computed tomography (SPECT) imaging of (131)I-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice.
In vitro cellular 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. (131)I-tRRL mainly accumulated in tumors in vivo, not other organs at 24 h after injection. SPECT imaging with (131)I-tRRL clearly visualized tumors in nude mice, especially at 24 h.
Radioiodinated 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.
探索一种靶向肿瘤细胞和肿瘤衍生内皮细胞（TDEC）的肿瘤肽成像剂精氨酸-精氨酸-亮氨酸（Tyr-Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys，三肽 RRL[tRRL]），并主要研究 tRRL 与血管内皮生长因子受体 2（VEGFR-2）之间的可能关系。
tRRL 序列基序被鉴定为与 TDEC 特异性结合的肿瘤分子标志物。将酪氨酸连接到 RRL（Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys）的氨基末端以进行放射性核素碘-131（131I-tRRL）标记。使用流式细胞术和放射性计数器在体外研究 tRRL 对肿瘤细胞和血管生成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 的结合位点。使用放射性核素碘-131（131I-tRRL）的生物分布和单光子发射计算机断层扫描（SPECT）成像来评估这种新的成像剂在评估裸鼠中不同肿瘤异种移植物的有效性。
体外细胞摄取实验表明，tRRL 不仅可以黏附在肿瘤血管生成内皮细胞上，而且还可以大量积累在恶性肿瘤细胞中。在 TDEC 上高度表达的 VEGFR-2 可能不是靶向肿瘤血管生成内皮细胞的 tRRL 的唯一结合配体。在注射后 24 小时内，131I-tRRL 主要在体内肿瘤中积累，而不在其他器官中积累。使用 131I-tRRL 进行 SPECT 成像可以清晰地在裸鼠中可视化肿瘤，尤其是在 24 小时时。
放射性碘标记的 tRRL 为靶向新生血管化的肿瘤功能分子成像提供了一种非侵入性核医学成像方法，可能是肿瘤放射免疫治疗载体的有前途的候选物。
