A rat model of leptomeningeal human neoplastic xenografts

Leptomeningeal (LM) cancer spread from either a primarybrain tumor or a systemic cancer is rapidlyfatal. Current therapies are ineffective and highly toxicto normal nervous system tissues. A xenograft modelof LM neoplasia in nude rats using adiversity of tumor cell types was established inorder to evaluate new treatment strategies and tostudy the pharmacokinetics and biological effects of treatmentsadministered into the subarachnoid space. Consistent leptomeningeal engraftmentand progressive tumor growth was seen after intrathecalinjection of 9 of 13 tumor cells lines,including 2 melanomas, 2 neuroblastomas, 2 medulloblastomas, 2gliomas, and 1 breast cancer. Clinical signs rangedfrom steady weight loss commencing from the dayafter tumor implantation to absence of any signsfor three weeks until the sudden occurrence ofmajor neurological deficits or death. Pathologic examination showedonly leptomeningeal tumor growth with some cell linesand severe parenchymal invasion with others. CSF cytologyconsistently demonstrated tumor cells in animals with LMdisease. Cranial magnetic resonance (MR) following intravenous (IV)administration of a contrast agent revealed enhancing lesionsone week following melanoma tumor implantation. Reliable ventricularpuncture was demonstrated by radiography following intraventricular (IVent)injection of an iodinated contrast material. IVent instillationof saline, albumin, or antibodies did not provokeclinical toxicity or an inflammatory response.