Ion Microscopy Imaging of 10Bfrom /7-Boronophenylalanine in a Brain Tumor Model for Boron Neutron Capture Therapy1

Boron neutron capture therapy (BNCT), a binary treatment modality that can potentially irradiate tumor tissue within cellular dimensions, is critically dependent on the preferential delivery of '"IS to individual neoplastic cells. In this study, ion microscopy was used to quantitatively evaluate the selectivity of p-boronophenylalanine-fructose (BPA-F) in the rat 9L gliosarcoma brain tumor model. With a spatial resolution of —¿ 0.5 /<m. ion microscopy images show that BPA-F delivers 3.5 times more boron to the main tumor mass [99 ±36 /ig/g tissue (mean ±SD)1 than to the contiguous normal brain (27 ±12 fig/g tissue). A similar, but lower, accumulation was observed away from the main tumor mass in small clusters of neoplastic cells (47 ±15 jug/g tissue) invading the surrounding brain ( 16 ±8 fig/g tissue). These findings establish for the first time the selectivity of BPA-F to the neoplastic cells invading the normal brain and provide a much-needed baseline measurement of the distribution of a clinically approved BNCT drug. Given the propensity for malignant brain tumors to infiltrate the surrounding normal brain, these observations have particular significance for clinical trials of BNCT for human glioblastoma multiforme using the drug BPA-F.