Ex vivo Evans blue assessment of the blood brain barrier in three breast cancer brain metastasis models
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The limited entry of anticancer drugs into the central nervous system represents a special therapeutic challenge for patients with brain metastases and is primarily due to the blood brain barrier (BBB). Albumin-bound Evans blue (EB) dye is too large to cross the BBB but can grossly stain tissue blue when the BBB is disrupted. The course of tumor development and the integrity of the BBB were studied in three preclinical breast cancer brain metastasis (BCBM) models. A luciferase-transduced braintropic clone of MDA-231 cell line was used. Nude mice were subjected to stereotactic intracerebral inoculation, mammary fat pad-derived tumor fragment implantation, or carotid artery injections. EB was injected 30 min prior to euthanasia at various timepoints for each of the BCBM model animals. Serial bioluminescent imaging demonstrated exponential tumor growth in all models. Carotid BCBM appeared as diffuse multifocal cell clusters. EB aided the localization of metastases ex vivo. Tumor implants stained blue at 7 days whereas gross staining was not evident until day 14 in the stereotactic model and day 28 for the carotid model. EB assessment of the integrity of the BBB provides useful information relevant to drug testing in preclinical BCBM models.
KeywordsBreast cancer brain metastasis Mouse brain metastasis model Blood brain barrier
We would like to thank Dr. Sanjiv Sam Gambhir for his technical support. This study was supported in part by the Komen for the Cure grant (KG090545), Small Animal Imaging Resource NIH-NCI ICMIC P50-CA114747-02 (Gambhir, PI), and Stanford University Cancer Center NIH NCI CCSG P30-CA124435-02 (Mitchell, PI).
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