TITLE:
In Vitro Evaluation System of Pharmacokinetics and Irradiation Effect in Boron Neutron Capture Therapy (BNCT) Using Three-Dimensional Artificial Human Tumor Tissue Model
AUTHORS:
Shintaro Ishiyama, Yoshiya Asano, Minoru Suzuki, Mitsuru Akashi, Hiroshi Shimoda
KEYWORDS:
Boron Neutron Capture Therapy (BNCT), Boronophenylalanine (10BPA), Artificial Human Tumor Tissue Model, Cell Accumulation Method
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.10 No.10,
October
21,
2019
ABSTRACT: Boron
neutron capture therapy (BNCT) is based on the incorporation of boron-containing drugs to cancer cells and the nuclear reaction of 10B
atoms by thermal neutron irradiation results 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 (10BPA) as a boron-containing drug
and neutron irradiation up to 2.52 × 1012 n/cm2 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) was 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.