Time-Dependent Biodistribution of BPA-F in Normal and Tumor Brain Tissues in Mice

Abstract

With the completion of the fission converter epithermal neutron beam (FCB) at MIT, BNCT irradiations conducted by the Harvard-MIT BNCT program could be reduced from approximately 2 1/2 hours per beam to a few minutes.1 Therefore, the timing of the irradiation becomes important. An optimal therapeutic gain is expected to be gained when patients are irradiated during a time window which has the best tumor/normal tissue 10B concentration ratio, and the boron concentration is high. Since in the current clinical trial, blood 10B concentration is used as a surrogate for normal brain tissue 10B concentration, while the metabolism of BPA-f in tumor and normal brain tissues is not well understood, it is important to determine the biodistribution and phar-macokinetics of boron in these tissues. In addition, to be able to prescribe accurate radiation dose to radiation sensitive areas such as the optic chiasm, knowledge of the spatial biodistribution of BPA-f in these tissues is essential. A GL261 murine glioma tumor model is being used to study in detail the time-dependent biodistribution of BPA-f in tumor and several anatomic sites in the normal brain. Preliminary results indicate that there are slight differences in the temporal uptake of BPA-f in different regions of the normal brain, and that the pharmacokinetics of BPA-f in GL261 tumor and normal brain are vastly different.