The further study on radioiodinated peptide Arg-Arg-Leu targeted to neovascularization as well as tumor cells in molecular tumor imaging

The importance of angiogenesis in tumor growth and metastasis has led to develop new imaging tracers to understand angiogenic vasculature. Based on the previous study, we further focused on the tumor molecular imaging application of the novel peptide Arginine-Arginine-Leucine (Tyr-Cys-Gly-Gly-Arg-Arg-Leu-Gly-Gly-Cys, tRRL) in this study. The cytotoxicity of raioiodinated tRRL (I-131-tRRL) in HepG2 cells was assessed by tested cell viability using kit. tRRL was conjugated with fluorescein FITC to observe its binding with tumor cells and human aortic endothelial cells (HAEC) in vitro. Whole body SPECT imaging of varied tumors xenograftes was performed after intravenous injection of I-131-tRRL for 24 h in BALB/c nude mice. Compared with negative control PBS, small peptide tRRL was of non-cytotoxicity. I-131-tRRL could lead to significant cytotoxicity on HepG2 cells when the radioactivity was greater than 370 kBq. In vitro binding experiment and cellular uptake results revealed that tRRL could adhere to tumor cells besides tumor derived endothelial cells. In vivo SPECT imaging, I-131-tRRL mainly accumulated in various tumor tissues, including melanoma, liver cancer and lung cancer bearing mice. In breast cancer xenografte imaging, the tumor has no significant radionuclide accumulation at 24 h after injected of I-131-tRRL. Radioiodinated tRRL offers a noninvasive nuclear imaging method for functional molecular imaging of tumors, and may be a promising candidate carrier for tumor targeted therapy.