title: Relationship between biodistribution of a novel thymidine phosphorylase (TP) imaging probe and TP expression levels in normal mice.
abstract: OBJECTIVE
  Thymidine phosphorylase (TP) is a key enzyme in the pyrimidine nucleoside salvage pathway and its expression is upregulated in a wide variety of solid tumors. In mice, we previously observed high and specific accumulation levels of our TP imaging probe, radioiodinated 5-iodo-6-[(2-iminoimidazolidinyl)methyl]uracil (IIMU) not only in high-TP-expressing tumors, but also in the liver and small intestine. To clarify the reason for the high accumulation levels of radioiodinated IIMU in the liver and small intestine, we investigated the expression levels of TP in mice in comparison with the biodistribution of radioiodinated IIMU ((123)I-IIMU).
  
  
  METHODS
  BALB/cCrSlc mice were injected with (123)I-IIMU, and the radioactivity levels [%ID/g (normalized to a mouse of 25 g body weight)] in the tissues of interest were determined 0.5, 1, 3 and 24 h after the injection (n = 5, each time point). To determine the expression levels of TP, BALB/cCrSlc and ddy mice (n = 3/each strain) were euthanized, and the heart, liver, lung, spleen, kidney, stomach, small intestine, large intestine and brain were collected. The mRNA and protein expression levels of TP in these organs were examined by quantitative reverse transcription-polymerase chain reaction and western blot analyses, respectively.
  
  
  RESULTS
  In BALB/cCrSlc mice administered (123)I-IIMU, markedly high radioactivity levels were observed in the liver [1.568 ± 0.237 (%ID/g)] and small intestine [0.506 ± 0.082 (%ID/g)], whereas those in the other tissues were fairly low [<0.010 ± 0.003 (%ID/g)] 30 min after the injection. The highest expression levels of TP mRNA were also observed in the liver and small intestine among the tissues tested. Immunoblotting showed intense immunoreactive bands of the TP protein for the liver and small intestine, whereas no notable bands were detected for other tissues. Similar expression profiles of TP mRNA and protein were observed in ddy mice.
  
  
  CONCLUSIONS
  We confirmed TP expression in various tissues of mice at the mRNA and protein levels: high TP expression levels were observed in the liver and small intestine. These high TP expression levels are consistent with the high accumulation levels of (123)I-IIMU in these tissues. Our results may provide important information about the physiological accumulation of (123)I-IIMU, which may be useful for the clinical diagnostic imaging of TP.
authors.affiliation: Department of Tracer Kinetics & Bioanalysis, Graduate School of Medicine, Hokkaido University, Kita 15 Nishi 7, Kita-ku, Sapporo, 060-8638, Japan, zsi@med.hokudai.ac.jp.
authors.forename: Songji
authors.initials: S
authors.lastname: Zhao
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Nishijima
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Akizawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Kazue
authors.initials: K
authors.lastname: Ohkura
authors.forename: Nagara
authors.initials: N
authors.lastname: Tamaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
mesh_terms: D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D057054:Molecular Imaging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013939:Thymidine Phosphorylase / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D014498:Uracil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: C551481:5-iodo-6-((2-iminoimidazolidinyl)methyl)uracil; D012333:RNA, Messenger; D014498:Uracil; D013939:Thymidine Phosphorylase