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(131I-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 131I-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.131I-tRRL mainly accumulated in tumors in vivo,not other organs at 24 h after injection.SPECT imaging with 131I-tRRL clearly visualized tumors in nude mice,especially at 24 h.Conclusion: 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.
