Use of Radioiodinated Peptide Arg-Arg-Leu Targeted to Neovascularization as well as Tumor Cells in Molecular Tumor Imaging

Objective： 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）. Methods： 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 （1311-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-tRRL were used to evaluate the effectiveness of this new imaging agent to visualize varied tumor xenografts in nude mice. Results： 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-tRRL mainly accumulated in tumors in vivo, not other organs at 24 h after injection. SPECT imaging with 131-tRRL clearly visualized tumors in nude mice, especially at 24 h. Conclusion： Radioiodinated tRRL offers a noninvasive of tumors targeted to neovascularization, and may be a carrier. nuclear imaging method for functional molecular imaging promising candidate for tumor radioimmunotherapeutic carrier,