Pharmacokinetics and metabolism of 5-125I-iodo-4'-thio-2'-deoxyuridine in rodents.

Abstract

UNLABELLED:

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.

CONCLUSION:

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.

• Authors: Jun Toyohara, Akie Gogami, Akio Hayashi, Yoshiharu Yonekura, Yasuhisa Fujibayashi
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 44 Issue 10 Pg. 1671-6 (Oct 2003) ISSN: 0161-5505 [Print] United States
• PMID: 14530485 (Publication Type: Journal Article)

Chemical References

• 5-iodo-4'-thio-2'-deoxyuridine
• Radiopharmaceuticals
• DNA
• Deoxyuridine

Topics

• Animals
• Blood (diagnostic imaging, metabolism)
• DNA (metabolism)
• Deoxyuridine (analogs & derivatives, blood, pharmacokinetics)
• Duodenum (diagnostic imaging, metabolism)
• Liver (diagnostic imaging, metabolism)
• Male
• Metabolic Clearance Rate
• Mice
• Mice, Inbred C57BL
• Organ Specificity
• Radionuclide Imaging
• Radiopharmaceuticals (blood, pharmacokinetics)
• Rats
• Rats, Sprague-Dawley
• Spleen (diagnostic imaging, metabolism)
• Thymus Gland (diagnostic imaging, metabolism)
• Tissue Distribution