β-Cyclodextrin Complexes of Hydrolyzable Adamantanoyl-IUdR Prodrugs - Radioiodination and Biodistribution in Mice Bearing Implanted KBALB Tumours
Purpose: Iododeoxyuridine (IUdR, 1), a thymidine mimic with antiviral and anti-cancer properties, has a very short in vivo half-life which limits its efficacy as a clinical therapeutic or diagnostic agent. This work reports the radioiodination of 1 and its adamantanoyl prodrugs 2 and
3, the β-cyclodextrin (β-CyD) complexation of the radiolabelled prodrugs (2* and 3* to β-CyD-2* and β-CyD-3*, respectively), and the biodistribution of 1*, β-CyD-2* and β-CyD-3* in tumor- bearing mice. Methods: The C-5-tributylstannyl-UdR
synthons 1-TBS, 2-TBS and 3-TBS were prepared and then radioiodinated with Na[125I]I in acetic acid and hydrogen peroxide to afford 125I-labelled 1*, 2* and 3*. Biodistribution studies of 1*, β-CyD-2* and β-CyD-3* were undertaken in Balb/c mice bearing implanted
KBALB tumours. Results: 1-TBS, 2-TBS and 3-TBS were synthesized in 70, 45 and 29 % yield, respectively. Radioiododestannylation afforded 1*, 2* and 3* in 25.5 %, 80 % and 45 % radiochemical yield, respectively. In vivo biodistribution patterns for 1*,
β-CyD-2* and β- CyD-3* after i.v. injection into mice differed only marginally. Conclusions: Inclusion complexes are formed between β- CyD and adamantane-IUdR conjugates. Despite the strong complexation between β-CyD and 2* or 3*, the radiobiodistribution patterns
of for 1*, β-CyD-2* and β-CyD-3* were not markedly different from each other in tumourbearing mice. Thus, despite creation of inclusion compounds with high dissociation constants, additional development is required to exploit the β-CyD inclusion complex approach for
improved delivery of nucleoside derivatives.
Keywords: KBALB tumours; adamantanoyl-nucleoside prodrugs; biodistribution; inclusion complexes; iododeoxyuridine; nucleosides; radioiodination; β-cyclodextrin
Document Type: Research Article
Publication date: 01 April 2009
- Current Radiopharmaceuticals publishes original research articles, letters, reviews, drug clinical trial studies and guest edited issues on all aspects of research and development of radiolabelled compound preparations. The scope of the journal covers the following areas: radio imaging techniques, therapies; preparation and application of radionuclide compounds including the incorporation of tracer methods used in scientific research and applications.
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