<i>In Vitro</i> Evaluation System of Pharmacokinetics and Irradiation Effect in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model

Abstract

Boron neutron capture therapy (BNCT) is based on the incorporation of boron - containing drugs to cancer cells and the nuclear reaction of 10 B atoms by thermal neutron irradiation result s in tumor degeneration. For the development of this therapy, currently , long time and high cost consuming experiments using many animals are required. In this study, we constructed a new in vitro evaluation system for BNCT by combination of an artificial tumor tissue model, comprised of normal human dermal-derived fibroblast (NHDF) and human pancreatic cancer cell line BxPC3, and the optical plastic material CR-39 as a solid state nuclear track detector. Administration of boronophenylalanine ( 10 BPA) as a boron - containing drug and neutron irradiation up to 2.52 × 10 12 n/cm 2 to the control tissue constructed by NHDF (NHDF3D) and BxPC3 cell loaded tissue (NHDF3D/BxPC3) resulted in detection of 1.6 times higher number of α -ray/recoiled Li particle tracks in NHDF3D/BxPC3 in comparison to NHDF3D, demonstrating that putative irradiation damage to cancer cells can be evaluated by this system. On a cellular level, the hit number of α -ray/recoiled Li particle tracks per single BxPC3 cells and NHDF was evaluated as 5.46 and 1.71, respectively. The tumor and normal tissue ratio (T/N ratio) w as 3.19, which was corresponded with those of BPA as 2 - 4 that reported in the previous studies. This new in vitro evaluation system may provide a useful tool for a low cost, labor - saving , and non-animal method for the development of new boron - containing drugs or improvement of BNCT conditions.