A Model for Brain Metastasis

Abstract

Numerous animal-brain tumor models have been developed to assist in choosing new chemotherapeutic agents for primary brain tumors (Bigner and Swenberg 1977). None can be used directly to test for hematogenous metastatic disease because each depends on direct tumor (or viral) implantation into the brain, which necessarily traumatizes the brain. In order (1) to circumvent the problem of mechanical disruption of brain tissue so as to examine chemotherapy and its relation to blood-brain barrier function in brain tumors, and (2) to develop a system to test agents specifically for metastatic brain tumors, my colleagues and I developed an animal model of metastatic brain tumor that does not require direct implantation into the brain (Ushio et al. 1977a). We have since used this model to test a series of chemotherapeutic agents, to begin an evaluation of the distribution of chemotherapeutic agents utilizing the marker molecule methotrexate, to examine the effects of radiation therapy, and to define the breakdown of the blood-brain barrier using α-aminoisobutyric acid. These studies are reviewed in this report.