Preparation and evaluation of (~(125)I)troxacitabine: L-nucleoside model of a potential agent for tumor diagnosis and radiotherapy

摘要

In this study, the optimization of troxacitabine labeling with iodine-125 and its biological evaluation were described. Troxacitabine was labeled via direct electrophilic substitution using chloramine-T as oxidizing agent. The optimum amounts of reactants were: 50 mug troxacitabine, 75 mug Chloramine-T and ~19kBq carrier free Na~(125)l. The labeled troxacitabine was stable for more than 24 h. Results of the in-vivo evaluation revealed that the new tracer, [~(125)I]troxacitabine, tends to localize in tissues with high proliferation rate with preferential accumulation in cancerous tissues. Imaging should be carried at 3 h postinjection. The in vitro cell growth inhibition assay showed that the effect of [~(125)I]troxacitabine was stronger than the effect of cold troxacitabine, which strongly suggested that its cytotoxicity was mainly due to radiotoxicity rather than chemotherapeutic activity. The binding assay revealed that I~(125)II]troxacitabine uptake by the Ehrlich and the ARAC8C cells was high and that it bounded well to DNA.