Collect. Czech. Chem. Commun. 2006, 71, 1051-1062

1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-[36Cl]chlorouracil; Radiosynthesis and Preliminary Biodistribution Studies in an Experimental Murine Tumor Model

Leonard I. Wiebe*, Edward E. Knaus, Takashi Iwashina, Hemant Misra and Yip W. Lee

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada, T6G 2N8


The nucleoside to nucleic acids pathways are attractive targets for molecular imaging of cell proliferation, for radionuclide-based radiotherapy, for following molecular processes and for drug design, development and delivery. This paper describes the preparation of several radiolabelled nucleosides for comparitive study as markers of tumour cell proliferation. 1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-[36Cl]chlorouracil (F[36Cl]ClAU)1 was synthesized by reaction of 1-(2-deoxy-2-fluoro-arabinofuranosyl)uracil (FAU) with Na36Cl in the presence of 2 M HNO3 (32% radiochemical yield; 13.5 MBq/mmol). 1-(2-Deoxy-2-fluoroarabinofuranosyl)-5-fluoro/bromo/iodouracils radiolabelled with carbon-14 ([2-14C]FFAU; 1.5 GBq/mmol), bromine-82 (F[82Br]BrAU; 167 MBq/mmol) and iodine-125 (F[125I]IAU; 10.4 GBq/mmol) were synthesized according to literature methods. These radiolabelled halopyrimidine nucleosides were administered by i.v. injection into BDF1 mice bearing transplanted Lewis Lung tumors. Uptake of test compounds by target (tumor) tissue was low, and not dissimilar to the reported uptake of their high-specific-activity 5-halopyrimidine nucleoside counterparts. Selected biodistribution data are presented. In general, clearance from blood was rapid, with less that one percent of the injected dose remaining in the blood within 1 h of injection. Tumor uptake was approximately 2% of the injected dose per g of tumor for F[36Cl]ClAU and F[125I]IAU, with [2-14C]FFAU showing less that 2% per g and F[82Br]BrAU with over 3% per g at this time after injection. Data are compared to those for the respective high-specific-activity counterparts.

Keywords: Radiosynthesis; Radioactive labelling; F[36Cl]ClAU; Antitumor drugs; Nucleosides; 5-Halopyrimidines; Biodistribution.

References: 40 live references.