Abstract
Here, we present a protocol for establishing a reproducible mouse model of brain metastasis. We describe the steps for preparing and injecting tumor cells into the internal carotid artery to achieve direct cerebral circulation delivery. We detail procedures for monitoring and validating brain colonization using magnetic resonance imaging (MRI) and histological analysis (H&E staining) and provide guidance on stereotactically generating, harvesting, and re-injecting intracranial tumors via the intracarotid route. This approach enables modeling of brain metastasis and tumor adaptation in the brain microenvironment.