Technetium-99m- Arg-Arg-Leu(g2), a modified peptide probe targeted to neovascularization in molecular tumor imaging.

Purpose: The 131I-tRRL small peptide probe has been identified in our previous study as a robust tumor molecular radiopharmaceutical that specifically binds to tumor-derived endothelial cells. In this study we developed a smaller structure cyclic tRRL (g2) radiolabeled with 99mTc as a novel and optimized peptide probe on tumor angiogenesis molecular imaging. Methods: Both tRRL (g2) and control peptide GGG (g2), as well as FITC-RRL (g2) and FITC-GGG (g2) peptide chains were synthesized and characterized by high performance liquid chromatography (HPLC) and electrospray ionization mass spectrometry (EMI-MS) analysis. After synthesis and purification, the peptides were radiolabeled with 99mTc by a one-step method for quantitative cell-binding assay and biodistribution experiments. A cell adhesion assay was performed to image tumor-derived endothelial cells-binding specificity with the novel RRL (g2) peptide probe in vitro. The biodistribution experiment was performed to show the tumor uptake of 99mTc-RRL (g2) compared with other tissues in human glioblastoma-bearing nude mice in vivo. Results: FITC-RRL (g2) had significantly higher tumor-derived endothelial cell-binding affinity and specificity than the control FITC-GGG (g2). 99mTc-RRL (g2) had higher tumor uptake (2,578 ± 0.293 at 30 min postinjection) and longer tumor retention than 99mTc-GGG (g2) in the tumor models tested. The tumor specificity of 99mTc-RRL (g2) was also confirmed by successful quantitative cell binding experiments. Conclusion: 99mTc-RRL (g2) has more good characteristics such as higher tumor uptake ratio and short half life time compared with 131I-tRRL. The information obtained here may guide the future development of RRL peptide-based tumor angiogenesis molecular imaging and internal radiotherapeutic agents targeting tumor neovascularity.