title: Synthesis and evaluation of Tc-99m-labeled RRL-containing peptide as a non-invasive tumor imaging agent in a mouse fibrosarcoma model.
abstract: OBJECTIVE
  Arginine-arginine-leucine (RRL) is considered a tumor endothelial cell-specific binding sequence. RRL-containing peptide targeting tumor vessels is an excellent candidate for tumor imaging. In this study, we developed RRL-containing hexapeptides and evaluated their feasibility as a tumor imaging agent in a HT-1080 fibrosarcoma-bearing murine model.
  
  
  METHODS
  The hexapeptide, glutamic acid-cysteine-glycine (ECG)-RRL was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling efficiency was evaluated using instant thin-layer chromatography. Uptake of Tc-99m ECG-RRL within HT-1080 cells was evaluated in vitro by confocal microscopy and cellular binding affinity was calculated. Gamma images were acquired In HT-1080 fibrosarcoma tumor-bearing mice, and the tumor-to-muscle uptake ratio was calculated. The inflammatory-to-normal muscle uptake ratio was also calculated in an inflammation mouse model. A biodistribution study was performed to calculate %ID/g.
  
  
  RESULTS
  A high yield of Tc-99m ECG-RRL complexes was prepared after Tc-99m radiolabeling. Binding of Tc-99m ECG-RRL to tumor cells had was confirmed by in vitro studies. Gamma camera imaging in the murine model showed that Tc-99m ECG-RRL accumulated substantially in the subcutaneously engrafted tumor and that tumoral uptake was blocked by co-injecting excess RRL. Moreover, Tc-99m ECG-RRL accumulated minimally in inflammatory lesions.
  
  
  CONCLUSIONS
  We successfully developed Tc-99m ECG-RRL as a new tumor imaging candidate. Specific tumoral uptake of Tc-99m ECG-RRL was evaluated both in vitro and in vivo, and it was determined to be a good tumor imaging candidate. Additionally, Tc-99m ECG-RRL effectively distinguished between cancerous tissue and inflammatory lesions.
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do, 570-711, Republic of Korea.|Research Unit of Molecular Imaging Agent (RUMIA), Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Republic of Korea.
authors.forename: Dae-Weung
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Research Unit of Molecular Imaging Agent (RUMIA), Wonkwang University School of Medicine, Iksan, Jeollabuk-do, Republic of Korea.
authors.forename: Woo Hyoung
authors.initials: WH
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do, 570-711, Republic of Korea.
authors.forename: Myoung Hyoun
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine and Institute of Wonkwang Medical Science, Wonkwang University School of Medicine, 344-2 Shinyong-Dong, Iksan, Jeollabuk-do, 570-711, Republic of Korea. akaxan@naver.com.
authors.forename: Chang Guhn
authors.initials: CG
authors.lastname: Kim
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D015902:Gamma Cameras; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018613:Microscopy, Confocal; D015394:Molecular Structure; D009132:Muscles / Q000000981:diagnostic imaging / Q000378:metabolism; D009368:Neoplasm Transplantation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051598:Whole Body Imaging
chemical_list: D009842:Oligopeptides; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C000609776:technetium 99m Glu-Cys-Gly-Arg-Arg-Leu
keywords: Arginine–arginine–leucine; RRL; Tc-99m; Tumor imaging