Xia Lu1, Lingzhou Zhao, Tian Xue, Huabei Zhang. 1. Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
Abstract
PURPOSE: The (131)I-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 (99m)Tc 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 (99m)Tc 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 (99m)Tc-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). (99m)Tc-RRL (g2) had higher tumor uptake (2,578 ± 0.293 at 30 min postinjection) and longer tumor retention than (99m)Tc-GGG (g2) in the tumor models tested. The tumor specificity of (99m)Tc-RRL (g2) was also confirmed by successful quantitative cell binding experiments. CONCLUSION: (99m)Tc-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.
PURPOSE: The (131)I-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 (99m)Tc 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 (99m)Tc 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 (99m)Tc-RRL (g2) compared with other tissues in humanglioblastoma-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). (99m)Tc-RRL (g2) had higher tumor uptake (2,578 ± 0.293 at 30 min postinjection) and longer tumor retention than (99m)Tc-GGG (g2) in the tumor models tested. The tumor specificity of (99m)Tc-RRL (g2) was also confirmed by successful quantitative cell binding experiments. CONCLUSION: (99m)Tc-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.