Development of in vivo models for studies of brain metastasis.

To develop an in vivo model for studies of brain metastasis, varying doses of K-1735 tumor cells with differing metastatic potentials were injected into the carotid arteries of anesthetized mice. Direct intracerebral administration of cells produced tumors in the brain parenchyma, and all tumor cells produced melanotic lesions at these sites. Studies with radioactively-labelled tumor cells confirmed that tumor cells reached the meninges and extracerebral organs. Distant metastases were found in the lungs and hearts of mice which received K-1735 cells into the carotid artery, but not in animals which received tumorigenic non-metastatic cells. Regardless of the type of cells injected, no growths were found in the meninges. The high degree of reproducibility recommends this model for studies designed to investigate the biology and therapy of cancer metastasis to the brain.