SYNTHESIS AND I-125 LABELING OF GLUCURONIDE COMPOUNDS FOR COMBINED CHEMO-THERAPY AND RADIOTHERAPY OF CANCER

Some types of cancer cells have high levels of beta-glucuronidase acti vity. This enzyme is able to deglucuronidate a variety of glucuronide derivatives on the cell membrane. Either O- or N-glucuronides can be s electively incorporated into the cancer cells. If the aglycone is cyto toxic, the glucuronide can potentially be used as a selective anti-can cer drug in cancers with high levels of beta-glucuronidase activity. N evertheless, in vitro studies carried out by various investigators hav e shown that the cytotoxicities of several glucuronides in cancer cell s are not sufficiently high for their use as effective anti-cancer dru gs. For this reason, we have synthesized glucuronide compounds radiola belled with iodine-125 combining the radiotoxicity of this Auger elect ron emitter with the chemotoxicity of the aglycone portion of the gluc uronide. (C) 1997 Elsevier Science Ltd.