INTRATHECAL 5-[I-125]IODO-2'DEOXYURIDINE IN A RAT MODEL OF LEPTOMENINGEAL METASTASES

The antitumor effect of 5-[I-125]iodo-2'-deoxyuridine ((125)IUdR) was examined in a rat model of leptomeningeal metastases. In this model, 5 0% of rats develop paralysis of hind limbs in 9.20 +/- 0.02 days and d ie in 12.1 +/- 2.1 days after intrathecal (i.t.) implantation of 5 x 1 0(5) 9L rat gliosarcoma cells. Methods: Three days after implantation of 9L gliosarcoma cells, (125)IUdR was administered intrathecally to r ats as: (a) a single injection (500 mu Ci/rat), (b) live daily injecti ons (100 mu Ci/day) or (c) a continuous 5-day infusion (0.5 mu l/hr, t otal of 500 mu Ci), and the animals were monitored for the onset of pa ralysis. Control groups received physiologic saline. For biodistributi on studies, rats received a bolus injection of (125)IUdR (10 mu Ci) 5 days after tumor-cell implantation and were killed 1, 8, 24, and 48 hr later. Tissues and organs, including the spinal cord, were isolated a nd their radioactive content determined. The results were expressed as percent injected dose per gram of wet tissue. Histological sections o f the spinal cord were also prepared and used for autoradiographic det ection of DNA-incorporated (125)IUdR. Results: Treatment with i.t. adm inistered (125)IUdR (500 mu Ci/rat) significantly (p less than or equa l to 0.005) prolonged the median time of paralysis to 11.2 +/- 0.1, 12 .3 +/- 0.1 and 15.2 +/- 0.4 days for the single-dose, five daily injec tions and continuous infusion groups, respectively. Radioactivity clea red rapidly from all tissues except the thyroid and tumor cells growin g within the spinal cord. Autoradiography demonstrated that normal cel ls in the tumor-bearing spinal cord were void of radioactivity Conclus ion: The results suggest that a selective antitumor effect could be ac hieved in treating leptomeningeal metastases with i.t. administered (1 25)IUdR.