title: In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging.
abstract: BACKGROUND
  The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis, tumor invasiveness and activation of antitumor agents. We evaluated radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil ([(125)I]IIMU) having high TP-inhibitory potency as the new radiotracer for SPECT targeting of TP expression in tumors.
  
  
  METHODS
  The characteristics of the radioiodinated TP inhibitor IIMU were determined by evaluating the uptake by tumor cells in vitro and by biodistribution studies in vivo. The distribution of the radiotracer and the extent of TP-specific uptake by tumors were evaluated by a counting method in tumor-bearing mice.
  
  
  RESULTS
  The in vitro uptake of radiolabeled IIMU by A431 cells along with high TP expressions was attributed to the binding of the radiotracer to its target enzyme, i.e., TP. In vivo distribution of the radiotracer in A431 tumor-bearing mice revealed tumor/blood and tumor/muscle activity uptake ratios of 36 and 106, respectively, at 3 h after the radiotracer injection. On using low TP-expressing tumors and TP blocking studies as controls, minor TP-specific accumulation of the radiotracer was detected in these studies.
  
  
  CONCLUSIONS
  According to the binding of radioiodinated IIMU to the angiogenic enzyme TP, it can be concluded that radioiodinated IIMU might be suitable as a SPECT tracer for tumor imaging.
authors.affiliation: Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Akizawa
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Seki
authors.forename: Kazue
authors.initials: K
authors.lastname: Ohkura
mesh_terms: D000818:Animals; D001692:Biological Transport; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007457:Iodine Radioisotopes; D051379:Mice; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging / Q000201:enzymology*; D013939:Thymidine Phosphorylase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon; D014498:Uracil / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: C551481:5-iodo-6-((2-iminoimidazolidinyl)methyl)uracil; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D014498:Uracil; D013939:Thymidine Phosphorylase