Bromophenol blue staining of tumors in a rat glioma model

OBJECTIVE: For patients with gliomas, decreasing the tumor burden with macroscopic surgical resection may affect quality of life, time to tumor progression, and survival. Injection of bromophenol blue (BPB) may enhance intraoperative Visualization of an infiltrating tumor and its margins and improve the extent of resection. In this study, we investigated the uptake of BPB in experimental rat brain tumors. METHODS: We first conducted a toxicity study with bolus intravenous injections of 5, 60, and 360 mg/kg doses of BPB in nontumor-bearing Fischer 344 rats. No adverse effects were observed in any of the animals during the 60 day observation period. We then injected 9L tumor cells intracerebrally into Fischer 344 rats and approximately 2 weeks later, administered a bolus intravenous injection of 5 to 360 mg/kg BPB. Fifteen minutes after BPB injection, we sacrificed the animals and removed their brains. In a subsequent study, we injected 180 rng/kg BPB and sacrificed animals at several time points to monitor tumor staining over time. RESULTS: The stain was clearly visible and localized to the tumor for all BPB concentrations 60 mg/kg or greater, and in an additional experiment, we found that tumor staining persisted for at least 8 hours after BPB injection. CONCLUSION: We conclude that BPB helped visualize experimental tumors at time points from a few minutes to several hours after injection. Because BPB also proved to be nontoxic to the animals at effective concentrations, we believe the compound may be potentially useful in helping neurosurgeons visualize brain tumors in humans.