Intrathecal 5-[125I]iodo-2'-deoxyuridine in a rat model of leptomeningeal metastases

The antitumor effect of 5-[125I]iodo-2'-deoxyuridine (125IUdR) was examined in a rat model of leptomeningeal metastases. In this model, 50% of rats develop paralysis of hind limbs. In 9.20 +/- 0.02 days and die in 12.1 +/- 2.1 days after intrathecal (i.t.) implantation of 5 x 10(5) 9L rat gliosarcoma cells.

Three days after implantation of 9L gliosarcoma cells, 125IUdR was administered intrathecally to rats as: (a) a single injection (500 microCi/rat), (b) five daily injections (100 microCi/day) or (c) a continuous 5-day infusion (0.5 microliter/hr, total of 500 microCi), and the animals were monitored for the onset of paralysis. Control groups received physiologic saline. For biodistribution studies, rats received a bolus injection of 125IUdR (10 microCi) 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 and their radioactive content determined. The results were expressed as percent injected dose per gram of wet tissue. Histological sections of the spinal cord were also prepared and used for autoradiographic detection of DNA-incorporated 125IUdR.

Treatment with i.t. administered 125IUdR (500 microCi/rat) significantly (p < or = 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 injections and continuous infusion groups, respectively. Radioactivity cleared rapidly from all tissues except the thyroid and tumor cells growing within the spinal cord. Autoradiography demonstrated that normal cells in the tumor-bearing spinal cord were void of radioactivity.

The results suggest that a selective antitumor effect could be achieved in treating leptomeningeal metastases with i.t. administered 125IUdR.