Project 1 The effect of boron neutron capture therapy on normal tissues (R3P1)

概要

INTRODUCTION: We have reported the results of overall survival (OS) following whole thoracic irradiation (WTI) with X-ray and thermal neutron beams derived from Kyoto University Research Reactor (KUR) in previous reports of “Progress Reports.”. In this year, we have carried out the experiment of WTI with boron using neutron capture irradiation (BNCR) boronophenyalanine (BPA). In this report, we reported the result of WTI with BNCR using BPA.

INTRODUCTION: Radiation-induced liver disease (RILD) is one of the fatal adverse events in radiation therapy. The mechanism of the RILD is still not clear. Boron neutron capture radiation (BNCR) can irradiate the cell fractions in which boron compounds distribute selectively since the path of heavy particles (4He and 7Li atoms) derived from boron neutron capture reaction are no-ticeably short ones less than 10 µm. To inves-tigate the mechanism of the RILD, BNCR is available for detecting the normal cell fractions which triggered to cause RILD. The objective of our study is to clarify the mechanism of radia-tion-induced liver injury using BNCR with bo-ron compounds selectively accumulating in normal cell fractions.

INTRODUCTION: Boron neutron capture therapy (BNCT) for liver tumor, which has been conducted up to the present, has used the compound effectiveness factor (CBE) determined by using genotoxicity for hepatocytes as an indicator, which has been clarified by Suzuki et al [1]. But there is a problem whether it is appropriate as a real clinical endpoint. Fundamental researches of liver fibrosis that are the late effect of radiation therapy are necessary. It is necessary to do basic research that uses liver fibrosis, which is a late radiation injury to the liver, as an evaluation index. The hedgehog signaling pathway is one of the important processes involved in animal de- velopment, and has been implicated in the maintenance and regeneration of adult tissues. The hedgehog signaling pathway is activated in the damaged liver and affects tissue remodeling. It has also been reported that cell pro- liferation is promoted and epithelial-mesenchymal transi- tion leading to fibrosis is induced [2]. A purpose of this study is to find the early indicator or surrogate marker which cause fibrosis in the normal liver tissue after BNCT.

INTRODUCTION: There are various tumors in which normal bone is in- cluded in the irradiation field, such as bone and soft tissue sarcoma, head and neck cancer, gynecologic cancer, pros- tate cancer, and tumors that have metastasized to the bone. As a result, radiation-induced bone toxicity, such as frac- ture, necrosis, and impairment of skeletal growth, can be occurred.
On the other hand, compared with the X-ray irradiation, boron neutron capture therapy (BNCT), a tumor cell -se- lective particle radiation therapy, is considered to be more effective without any late effects to the normal bone. How- ever, to apply BNCT to the clinical practice, accurate do- simetry is essential. And the compound biological effec- tiveness (CBE) factor, the value which is necessary when converting to the X-ray equivalent dose, is significant for this purpose.
In this project, we had elucidated the CBE factor of nor- mal bone by evaluating the influence on bone strength in mice. Furthermore, the boron concentrations in whole bones after the administration of the boron compound were analyzed. In this year, we visualized the 10B bio-dis- tribution to investigate the BNCT-specific reduction of bending strength.

INTRODUCTION: There are various tumors in which normal bone is in- cluded in the irradiation field, such as bone and soft tissue sarcoma, head and neck cancer, gynecologic cancer, pros- tate cancer, and tumors that have metastasized to the bone. In particular, there is a high incidence of bone tumors such as osteosarcoma, chondrosarcoma and Ewing’s sarcoma in the adolescent and young adult generation. As a result, ra- diation-induced bone toxicity, such as fracture, necrosis, and impairment of skeletal growth, can be occurred.
On the other hand, compared with the X-ray irradiation, boron neutron capture therapy (BNCT), a tumor cell-se- lective particle radiation therapy, is considered to be more effective without any late effects to the normal bone. How- ever, in our previous study using the adult mice, the higher accumulation was seen in the epiphyseal cartilage includ- ing the growth plate. This finding indicates that the higher radiation doses might be delivered to the growth plate and may cause the impairment of skeletal growth.
In this project, we investigate the biological behavior of boron compound in the normal tibia of young mice, in- cluding the analysis of the boron concentration and the bio-distribution of administered boron compound. Fur- thermore, BNCT was performed on the bones of young mice to evaluate their influence 3 months after the irradia- tion.

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