l-(2-DEOXY-2-FLUORO-beta-D-ARABINOFURANOSYL)-5-[~(36)Cl]-CHLOROURACIL;RADIOSYNTHESIS AND PRELIMINARY BIODISTRIBUTION STUDIES IN AN EXPERIMENTAL MURINE TUMOR MODEL

摘要

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.l-(2-Deoxy-2-fluoro-P-D-arabinofuranosyl)-5-[~(36)Cl]chlorouracil (F[~(36)C1]C1AU)was synthe-sized by reaction of l-(2-deoxy-2-fluoro-arabinofuranosyl)uracil (FAU)with Na~(36)Cl in the presence of 2 M HNO_3 (32% radiochemical yield;13.5 MBq/mmol).l-(2-Deoxy-2-fluoro-arabinofuranosyl)-5-fluoro/bromo/iodouracils radiolabelled with carbon-14 ([2-~(14)C]FFAU;1.5 GBq/mmol),bromine-82 (F[~(82)Br]BrAU;167 MBq/mmol)and iodine-125 (F[~(125)I]IAU;10.4 GBq/mmol)were synthesized according to literature methods.These radiolabelled halopyrimdine nucleosides were administered by i.v.injection into BDF_1 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-halo-pyrimidine 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[~(36)C1]C1AU and F[~(125)I]IAU,with [2-~(14)C]FFAU showing less that 2% per g and F[~(82)Br]BrAU with over 3% per g at this time after injection.Data are compared to those for the respective high-specific-activity counterparts.