5-[I-125]IODO-2'-DEOXYURIDINE IN THE RADIOTHERAPY OF BRAIN-TUMORS IN RATS

Glial neoplasms of the human central nervous system have defied treatm ent, in part because of the limited selectivity of available cytotoxic agents. The thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter I-125 ((125)IUdR) is highly toxic to divid ing cells when it is deoxyribonucleic acid incorporated, but it is rel atively innocuous when located outside the nucleus. Previous studies h ave shown that (125)IUdR has significant antineoplastic potential agai nst mammalian cells in vitro and direct administration of (125)IUdR is effective therapy for ovarian ascites tumors in mice and neoplastic m eningitis in rats. Studies using external gamma imaging and autoradiog raphy have also shown that direct intratumoral administration of (123) IUdR/(125)IUdR into intracerebral 9L gliosarcomas in rats results in s elective uptake of the radionuclide into tumor cells. Based on these e ncouraging results, we have evaluated the therapeutic potential of (12 5)IUdR in rats bearing intracerebral 9L gliosarcomas. Methods: iodino- 125-IUdR was infused intracerebrally over a 2-day period into rats bea ring 1-day-old 9L tumors and over a 6-day period into animals with 9-d ay-old 9L tumors; equimolar concentrations oi (127)IUdR were infused i nto control animals. Tumor growth was monitored by contrast-enhanced H -1 MRI and animal survival was followed over time. Results: Intracereb ral tumors (3-7 mm) were readily detected by MRI. Tumor-bearing rats t reated with (127)IUdR succumbed within 17-24 days, whereas tumor-beari ng animals treated with (125)IUdR survived significantly longer, and 1 0%-20% of the animals were cured of tumors. Conclusion: These data sub stantiate the antineoplastic potential of 5-[I-125]iodo-2'-deoxyuridin e and indicate that it may be a useful agent for the therapy of solid tumors that are accessible to direct radiopharmaceutical administratio n.