Abstract
According to the Ministry of Health and Welfare, oral cancer was the fifth most common throughout the population in 2013. Oral cancer has a high recurrence rate and frequently metastasizes to cervical lymph nodes. Lymph node metastasis has a poor prognosis and is a prognostic index for oral cancer. Boron neutron capture therapy (BNCT) is a promising new modality for cancer treatment. In BNCT, boronophenylalanine (BPA) accumulates in a tumor, while being present at a much lower level in a normal tissue. After boron drug treatment, the tumor is irradiated with thermal neutron inducing α-particles and 7Li. These two particles have a high linear energy transfer. All of their energy is deposited in cells, effectively killing tumor cells while doing little damage to normal tissue. The therapeutic success of BNCT depends on the high boron concentration in the tumor, the high tumor-to-the normal tissue boron ratio, the homogenous distribution of boron in the tumor and the high-quality thermal neutron beam. Therefore, this involves a series of investigations to evaluate the therapeutic effect of BPA-mediated BNCT against oral cancer. The program has four parts. In Part I.a, low dose of gamma irradiation enhances boronophenylalanine uptake in head and neck carcinoma cells for boron neutron capture therapy. In Part I.b, the boron concentration is increased in the tumor using low-dose gamma radiation to improve the therapeutic efficiency of BPA-mediated BNCT in an orthotopic oral cancer animal model. In Part II, the pharmacokinetics and tumor to normal tissue boron ratios are obtained by 18F-BPA-PET scan before BNCT and that obtained by ICP-AES analysis following real-time BNCT treatment in an orthotopic oral cancer model. In Part III, macro- and micro-distributions of BPA are analyzed in a subcutaneous xenograft model for BNCT. In Part IV, the administration of BPA is optimized to maintain a high boron concentration in tumor and narrow down the range of normal tissue to blood boron ratios in BNCT in a mouse model.