title: Technetium-99m- Arg-Arg-Leu(g2), a modified peptide probe targeted to neovascularization in molecular tumor imaging.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  (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.
authors.affiliation: Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Lu
authors.forename: Lingzhou
authors.initials: L
authors.lastname: Zhao
authors.forename: Tian
authors.initials: T
authors.lastname: Xue
authors.forename: Huabei
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D017076:Computer-Aided Design; D042783:Endothelial Cells / Q000000981:diagnostic imaging / Q000378:metabolism; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006207:Half-Life; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D062105:Molecular Docking Simulation; D057054:Molecular Imaging / Q000379:methods*; D009389:Neovascularization, Pathologic; D009842:Oligopeptides / Q000138:chemical synthesis / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D014018:Tissue Distribution; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C583847:technetium 99m arginyl-arginyl-leucine; D040301:Vascular Endothelial Growth Factor Receptor-2