Evaluation of the distribution of the boron neutron capture therapy drug 4-borono-L-phenylalanine (BPA) in a rat brain tumor model using liquid chromatography/tandem mass spectrometry (LC-MS/MS)

The blood-brain barrier (BBB) restricts drug delivery to the brain. Although recent advancements have led to the development of drugs designed to bypass the BBB, the treatment of neurological disorders remains a clinical challenge. In this study, we quantitatively evaluated the distribution of 4-borono-L-phenylalanine (BPA), a drug used in boron neutron capture therapy (BNCT), in brain tumors. Recent findings have shown that the BBB exhibits heterogeneity in drug uptake, particularly in the context of brain tumors, which often leads to treatment failure and/or recurrence. Understanding the heterogeneity of the BBB is crucial to facilitate effective drug delivery and treatment of brain tumors using BNCT. Herein, we performed boron distribution mapping in 26 brain segments from a rat model of metastatic melanoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The boron concentrations measured using LC-MS/MS in tumor and cerebral cortex samples were relatively close to those obtained via inductively-coupled plasma atomic emission spectrometry (ICP-AES) under the same administration conditions, suggesting that the measurements obtained with LC-MS/MS were plausible. The boron distribution in the tumor, obtained by LC-MS/MS, suggested heterogeneous accumulation. In our next study, we will investigate a method to determine the BPA concentration in smaller samples (less than 1 mg) or lower concentration of BPA in order to capture the characteristics of tumor heterogeneity in detail.