Abstract |
1-(2-Deoxy-beta-D-ribofuranosyl)-2,4-difluoro-5-iodobenzene (dRFIB) is a putative bioisostere of iododeoxyuridine ( IUdR). The advantages of dRFIB over IUdR for in vivo studies include resistance to both phosphorolytic cleavage of the nucleoside bond and de-iodination. dRFIB was radioiodinated (dRF(123/125)IB) by copper-catalyzed exchange using commercial sodium [(123/125)I] iodide. The in vivo biodistribution of dRF[(125)I]IB in BALBc mice and imaging of dRF[(123)I]IB in Sprague-Dawley rats are reported. In vivo data for rats show rapid clearance of radioactivity from blood (>95%ID in 15 minutes), extensive excretion in urine (56%ID/24 hours), concentration in the hepatobiliary-small intestine system and very little fecal excretion (approximately 3%ID/24 hours). Pharmacokinetic data for dRF[(125)I]IB (i.v. 48.7 ug/kg) in rats (t(1/2)[h] = 0.51 +/- 0.14, AUC(inf)[microg.min/mL] = 3.7 +/- 0.4, Cl[L/kg/h] = 0.75 +/- 0.12, Vss[L/kg] = 0.96 +/- 0.18) confirm previously reported dose-dependent pharmacokinetics. Scintigraphic images of rats dosed with dRF[(123)I]I were compatible with rapid soft-tissue clearance and extensive accumulation of radioactivity in bladder/urine and liver/small intestine. In tumor-bearing mice, thyroid and stomach radioactivity was indicative of moderate deiodination. An unidentified polar radioactive metabolite was detected in serum.
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Authors | Anke Stahlschmidt, Panteha Khalili, William Sun, Hans-Jürgen Machulla, Edward E Knaus, Leonard I Wiebe |
Journal | Nucleosides, nucleotides & nucleic acids
(Nucleosides Nucleotides Nucleic Acids)
Vol. 28
Issue 5
Pg. 379-93
(May 2009)
ISSN: 1532-2335 [Electronic] United States |
PMID | 20183590
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 1-(2-deoxyribofuranosyl)-2,4-difluoro-5-iodobenzene
- Deoxyribonucleosides
- Radioisotopes
- Thymidine
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Topics |
- Animals
- Deoxyribonucleosides
(pharmacokinetics)
- Male
- Mice
- Mice, Inbred BALB C
- Neoplasms
(diagnosis)
- Radioisotopes
(pharmacokinetics)
- Radionuclide Imaging
- Rats
- Rats, Sprague-Dawley
- Thymidine
(analogs & derivatives)
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