Colon-specific Prodrugs of 5-radioiodo-2′-deoxyuridine

Janina Baranowska-Kortylewicz, Zbigniew P. Kortylewicz, Debra Hoffman, Anna Winoto, Jing Lai, Glenn V. Dalrymple

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Two glycoside-based prodrugs, 125IUdR-5′-β-D-glucopyranoside and 125IUdR-5′-β-D-galactopyranoside, were synthesized. This selection was dictated by the abundance of appropriate enzymes in the GI tract of mice and similar levels of β-D-glycosidases in human and rodent large intestine. Studies to establish the ability of colonic microflora to release 125IUdR were conducted in vitro and in Swiss Webster mice. Both prodrugs released 125IUdR in the presence of the corresponding enzymes or the GI content homogenates in vitro, and in vivo. Luminal enzymes in the proximal and distal small intestine in mice degraded less than 10% of each prodrug whereas enzymes from the colonic/caecal lumen of mice released nearly 100% of 125IUdR. 125IUdR freed by bacterial glycosidases was stable in the GI content. No significant amounts of other metabolites or deiodination products were observed. Total radioactivity recovered as by-products was less than 10%. The efflux of prodrugs from the GI tract after oral administration in mice was slow and limited. Unlike 125IUdR, prodrugs were not dehalogenated in vivo as indicated by biodistribution and imaging studies.

Original languageEnglish (US)
Pages (from-to)959-964
Number of pages6
JournalActa Oncologica
Volume35
Issue number7
DOIs
StatePublished - 1996

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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    Baranowska-Kortylewicz, J., Kortylewicz, Z. P., Hoffman, D., Winoto, A., Lai, J., & Dalrymple, G. V. (1996). Colon-specific Prodrugs of 5-radioiodo-2′-deoxyuridine. Acta Oncologica, 35(7), 959-964. https://doi.org/10.3109/02841869609104052