Synthesis and iodine-125 labelling of glucuronide compounds for combined chemo- and radiotherapy of cancer

Some types of cancer cells have high levels of beta-glucuronidase activity. This enzyme is able to deglucuronidate a variety of glucuronide derivatives on the cell membrane. Either O- or N-glucuronides can be selectively incorporated into the cancer cells. If the aglycone is cytotoxic, the glucuronide can potentially be used as a selective anti-cancer drug in cancers with high levels of beta-glucuronidase activity. Nevertheless, in vitro studies carried out by various investigators have shown that the cytotoxicities of several glucuronides in cancer cells are not sufficiently high for their use as effective anti-cancer drugs. For this reason, we have synthesized glucuronide compounds radiolabelled with iodine-125 combining the radiotoxicity of this Auger electron emitter with the chemotoxicity of the aglycone portion of the glucuronide. (C) 1997 Elsevier Science Ltd.