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

Journal of Nuclear Medicine

Akio Hayashi¹  Yasuhisa Fujibayashi¹  Akie Gogami¹  Jun Toyohara¹  Yoshiharu Yonekura¹ 

关键词: pharmacokinetics;    metabolite;    5-¹²⁵I-iodo-4′-thio-2′-deoxyuridine;    DNA synthesis;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

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.

【 授权许可】

Unknown