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Cisterna Magna Injection Approach for the Treatment of Leptomeningeal Metastatic Brain Tumors

Zhenhua Xu1, Najiba Murad1, Yanxin Pei1

Abstract

Leptomeningeal metastases (LM) in the setting of pediatric brain tumors are associated with particularly poor prognosis. Current therapies for pediatric brain tumors include surgery, radiation, and chemotherapy. However, LM are not amenable to surgical resection and frequently do not respond to radiation. Moreover, most chemotherapeutic drugs are unable to cross the blood-brain barrier or blood-cerebrospinal fluid (CSF) barrier to reach LM. Here, we describe a mouse model of pediatric brain tumors that develop LM and an easy, reproducible approach to deliver therapeutic agents to treat LM. We intrathecally injected a CSF tracer via the cisterna magna in mice. After a single injection, the CSF tracer influx was observed along the leptomeninges throughout the entire central nervous system and persisted for at least 6 hours. Daily injection did not result in apparent toxicity or impact animal weight. The results of this study highlight the utility of a mouse model of metastatic pediatric brain tumors as well as the potential application of a repeated intrathecal injection technique to deliver therapeutic agents to treat metastatic brain tumors.

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