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Pharmacokinetics and Metabolism of 5-¹²⁵I-Iodo-4'-Thio-2'-Deoxyuridine in Rodents

¹ Research and Development Division, Research Center, Nihon Medi-Physics Co., Ltd., Chiba, Japan
² Biomedical Imaging Research Center, Fukui Medical University, Fukui, Japan

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 ¹²⁵I-ITdU into DNA. Results: The blood distribution study suggested the influx of ¹²⁵I-ITdU into rat peripheral blood cells. The blood metabolism of ¹²⁵I-ITdU in vitro was negligible. Plasma analysis at 60 min after injection showed that 50% of the radioactivity was intact ¹²⁵I-ITdU. The plasma clearance of ¹²⁵I-ITdU showed a biexponential function with half-lives of 0.2 and 29.5 min, representing 94.2% and 5.8% of plasma ¹²⁵I-ITdU concentration, respectively. ¹²⁵I-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. Conclusion: These data demonstrate that ¹²⁵I-ITdU is less susceptible against catabolism and readily incorporated into DNA in proliferating tissues. Therefore, ¹²⁵I-ITdU may be useful in measuring DNA synthesis with SPECT.

Key Words: pharmacokinetics • metabolite • 5-¹²⁵I-iodo-4'-thio-2'-deoxyuridine • DNA synthesis

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