Leptomeningeal metastasis (LM) is a difficult management problem of patients with various types of cancers. If left untreated, it is invariably fatal. There is essentially no effective treatment. Serious untoward effects are associated with current therapies including neural-axis irradiation and/or intrathecal chemotherapy. The former is limited by radiotoxicity to the underlying nervous tissues while the latter, by intrathecal breakdown and poor penetration of the meninges to reach the tumors. On the other hand, the locoregional use of radiopharmaceuticals such as beta-emitters with millimeter ranges may overcome such hurdles. Beta emission from iodine-131 has a limited range of 2-3 mm that is not impeded by diffusion. It will deliver large radiation to the tumors in the CSF and meninges while sparing the cerebral cortices and the spinal cord. Others using tumor-specific I-131 labeled anti-tenascin monoclonal antibodies have found partial therapeutic success but encountered hematotoxicity. Since hematotoxicity from I-131 compounds has been correlated with total body exposure and labeled antibodies are known to be retained in the body for days, exclusion of the antibody moiety may enhance excretion of unnecessary radiopharmaceuticals and decrease hematotoxicity to allow higher initial dosage for better efficacy. This study aims to determine the regional distribution, dosimetry, potential toxicity and efficacy of intrathecal I-131 sodium iodide (NaI). It is a widely available radiopharmaceutical for effective thyroid cancer therapy. Our preliminary modeling results have found sufficient dosimetry to treat tumor cells in the CSF and meninges, while sparing the underlying brain and spinal cord. This Phase I study will measure the whole-body, organ and regional dosimetry of intrathecally injected I- 131 NaI to correlate with potential efficacy and side effects including thyrotoxicity, hematotoxicity and neurotoxicity. Five to six groups of 3 patients will be studied according to the IRB-approved protocol ID98- 331. In brief, study patients will undergo intrathecal injection of I-131 NaI, followed by blood and urine collection and scintigraphic imaging at determined intervals for pharmacokinetics and dosimetry. Eradication of tumor cells in the CSF will be the primary indicator of efficacy. The CSF cytology, MRI, thyroid, hematology and neuropsychology profiles and neurological status will be followed up to 6 months and contrasted with dosages and dosimetry to determine a reliable set of parameters for further studies. At the end of the study period, our team shall have generated a sufficient set of data to determine whether it is worthwhile to pursue a phase II clinical trial of intrathecal I-131 NaI for the treatment of LM.
