Pharmacokinetics and metabolism of 5-125I-iodo-4'-thio-2'-deoxyuridine in rodents.
Pharmacokinetics and metabolite analysis of radioiodinated 5-iodo-4'-thio-2'-deoxyuridine (ITdU), a potential tumor cell proliferation-imaging agent, were investigated in rodents.


METHODS
Blood and urine metabolites of radiolabeled ITdU were analyzed by thin-layer chromatography in rats. Tissue fractionation studies in mice were also performed to investigate the incorporation of (125)I-ITdU into DNA.


RESULTS
The blood distribution study suggested the influx of (125)I-ITdU into rat peripheral blood cells. The blood metabolism of (125)I-ITdU in vitro was negligible. Plasma analysis at 60 min after injection showed that 50% of the radioactivity was intact (125)I-ITdU. The plasma clearance of (125)I-ITdU showed a biexponential function with half-lives of 0.2 and 29.5 min, representing 94.2% and 5.8% of plasma (125)I-ITdU concentration, respectively. (125)I-ITdU was excreted in urine 86% intact at 3.5 h after injection. Extraction of the tissues demonstrated that >70% of the activity in the duodenum, spleen, and thymus was incorporated into DNA at 8 h after injection. On the other hand, <8% of the activity in the liver was in the DNA fraction at that time.


CONCLUSIONS
These data demonstrate that (125)I-ITdU is less susceptible against catabolism and readily incorporated into DNA in proliferating tissues. Therefore, (125)I-ITdU may be useful in measuring DNA synthesis with SPECT.
Toyohara
Jun
J
Research and Development Division, Research Center, Nihon Medi-Physics Co., Ltd., Chiba, Japan.
Gogami
Akie
A
Hayashi
Akio
A
Yonekura
Yoshiharu
Y
Fujibayashi
Yasuhisa
Y
D000818:Animals; D001769:Blood / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics*; D004386:Duodenum / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000000981:diagnostic imaging / Q000378:metabolism; D013950:Thymus Gland / Q000000981:diagnostic imaging / Q000378:metabolism; D014018:Tissue Distribution
C465667:5-iodo-4'-thio-2'-deoxyuridine; D019275:Radiopharmaceuticals; D004247:DNA; D003857:Deoxyuridine