A rat model of leptomeningeal human neoplastic xenografts

Leptomeningeal (LM) cancer spread from either a primary brain tumor or a systemic cancer is rapidly fatal. Current therapies are ineffective and highly toxic to normal nervous system tissues. A xenograft model of LM neoplasia in nude rats using a diversity of tumor cell types was established in order to evaluate new treatment strategies and to study the pharmacokinetics and biological effects of treatments administered into the subarachnoid space. Consistent leptomeningeal engraftment and progressive tumor growth was seen after intrathecal injection of 9 of 13 tumor cells lines, including 2 melanomas, 2 neuroblastomas, 2 medulloblastomas, 2 gliomas, and 1 breast cancer. Clinical signs ranged from steady weight loss commencing from the day after tumor implantation to absence of any signs for three weeks until the sudden occurrence of major neurological deficits or death. Pathologic examination showed only leptomeningeal tumor growth with some cell lines and severe parenchymal invasion with others. CSF cytology consistently demonstrated tumor cells in animals with LM disease. Cranial magnetic resonance (MR) following intravenous (i.v.) administration of a contrast agent revealed enhancing lesions one week following melanoma tumor implantation. Reliable ventricular puncture was demonstrated by radiography following intraventricular (IVent) injection of an iodinated contrast material. IVent instillation of saline, albumin, or antibodies did not provoke clinical toxicity or an inflammatory response.