title: A novel 99mTc-labeled molecular probe for tumor angiogenesis imaging in hepatoma xenografts model: a pilot study.
abstract: BACKGROUND
  Visualization of tumor angiogenesis using radionuclide targeting provides important diagnostic information. In previous study, we proved that an arginine-arginine-leucine (RRL) peptide should be a tumor endothelial cell specific binding sequence. The overall aim of this study was to evaluate whether (99m)Tc-radiolabeled RRL could be noninvasively used for imaging of malignant tumors in vivo, and act as a new molecular probe targeting tumor angiogenesis.
  
  
  METHODS
  The RRL peptide was designed and radiosynthesized with (99m)Tc by a one-step method. The radiolabeling efficiency and radiochemical purity were then characterized in vitro. (99m)Tc-RRL was injected intravenously in HepG2 xenograft-bearing BALB/c nude mice. Biodistribution and in vivo imaging were performed periodically. The relationship between tumor size and %ID uptake of (99m)Tc-RRL was also explored.
  
  
  RESULTS
  The labeling efficiencies of (99m)Tc-RRL reached 76.9% ± 4.5% (n = 6) within 30-60 min at room temperature, and the radiochemical purity exceeded 96% after purification. In vitro stability experiment revealed the radiolabeled peptide was stable. Biodistribution data showed that (99m)Tc-RRL rapidly cleared from the blood and predominantly accumulated in the kidneys and tumor. The specific uptake of (99m)Tc-RRL in tumor was significantly higher than that of unlabeled RRL blocking and free pertechnetate control test after injection (p<0.05). The ratio of the tumor-to-muscle exceeded 6.5, tumor-to-liver reached 1.98 and tumor-to-blood reached 1.95. In planar gamma imaging study, the tumors were imaged clearly at 2-6 h after injection of (99m)Tc-RRL, whereas the tumor was not imaged clearly in blocking group. The tumor-to-muscle ratio of images with (99m)Tc-RRL was comparable with that of (18)F-FDG PET images. Immunohistochemical analysis verified the excessive vasculature of tumor. There was a linear relationship between the tumor size and uptake of (99m)Tc-RRL with R(2) = 0.821.
  
  
  CONCLUSIONS
  (99m)Tc-RRL can be used as a potential candidate for visualization of tumor angiogenesis in malignant carcinomas.
authors.affiliation: Department of Nuclear Medicine, Peking University First Hospital, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.forename: Ping
authors.initials: P
authors.lastname: Yan
authors.forename: Rong Fu
authors.initials: RF
authors.lastname: Wang
authors.forename: Chun Li
authors.initials: CL
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Yin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D009842:Oligopeptides / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D010865:Pilot Projects; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D014018:Tissue Distribution; D047368:Tumor Burden
chemical_list: D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C583847:technetium 99m arginyl-arginyl-leucine