In vitro and in vivo evaluations of a radioiodinated thymidine phosphorylase inhibitor as a tumor diagnostic agent for angiogenic enzyme imaging.
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.
Akizawa
Hiromichi
H
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Hokkaido 061-0293, Japan.
Zhao
Songji
S
Takahashi
Masayuki
M
Nishijima
Ken-ichi
K
Kuge
Yuji
Y
Tamaki
Nagara
N
Seki
Koh-ichi
K
Ohkura
Kazue
K
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
C551481:5-iodo-6-((2-iminoimidazolidinyl)methyl)uracil; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D014498:Uracil; D013939:Thymidine Phosphorylase