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Project 4 The effect of boron neutron capture therapy on normal tissues (R2P4)

Suzuki, M 京都大学

2021.08

概要

P4-1: “The effect of boron neutron capture therapy (BNCT) on normal lung in mice.”
 The effect of thermal neutron beam at KUR on nor- mal lung was analyzed with reference to the survival. The mice were sorted into four treatment groups, 40- min, 50-min, 60-min, and 70-min irradiation groups. In each group, six to seven mice were irradiated. In 70-min irradiation group, all the three mice died within 10 days. In 60-min irradiation group, six mice died within an observation period of 12 days, and three mice survive within an observation period of 380 to 540 days. In 50-min irradiation groups, five mice died, and two mice survived within an observation period of 451 to 570 days. In 40-min irradiation groups, two mice died, and five mice survived within an observation period of 465 to 577 days.

P4-2: “Clarification of the normal cell fractionation as a trigger for radiation-induced liver injury.”
 The objective of our study is to clarify the mechanism of radiation-induced liver injury.
We used the following boron cluster-sugar chain-con- jugated albumin.
・Asialo-N-glycan-HSA-10B
・Mannose-N-glycan-HSA-10B
・Hybrid-N-glycan-HSA-10B
 The sugar chains recognize the normal tissue compo- nents, hepatocytes, and non-parenchymal cells. We an- alyzed boron spatial distribution using autoradiography technique.

P4-3: “The Effect of Boron Neutron Capture Ther- apy to Normal Bones in Mice.”
 Cognitive impairment and radiation brain necrosis are late adverse effects after radiation therapy against brain or head and neck tumors. Biological effect of Boron Neutron Capture therapy (BNCT) on central nervous system is unknown. To avoid thosu late adverse effects,
 We investigate the biological effects of BNCT on neu-ronal cells and brain blood vessels. We used human iPSC-derived Neural stem/progenitor cell (NSPC) lines and blood-brain barrier (BBB) model composed of rat brain capillary endothelial cells, pericytes, and astro- cytes.
 In neuronal cells, early apoptosis was not detected af- ter 24 hours after BNCT. Frequency of Necrosis occur- rence did not increase with increasing BPA concentra- tion.

P4-5: “The Effect of Boron Neutron Capture Ther- apy to Normal Bones in Mice.”
 In this project, we have performed X-ray or neutron irradiation to normal tibial bone in mice with and with- out boronophenylalanine (BPA) and determined the compound biological effectiveness (CBE) factor for BPA as the biological endpoint of the tibial bending strength.

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参考文献

PR4-2

[1] Kikuchi S, Kanoh D, Sato S, Sakurai Y, Suzuki M, Nakamura H. Maleimide-functionalized closo-dodecaborate albumin conjugates (MID-AC): Unique ligation at cysteine and lysine residues enables efficient boron delivery to tumor for neutron capture therapy. J Control Release 2016;237:160–7. https://doi.org/10.1016/j.jconrel.2016.07.017.

[2] Ogura A, Tahara T, Nozaki S, Morimoto K, Kizuka Y, Kitazume S, et al. Visualizing Trimming Dependence of Biodistribution and Kinetics with Homo-and Heterogeneous N-Glycoclusters on Fluorescent Albumin. Sci Rep 2016;6. https://doi.org/10.1038/srep21797.

[3] Takeno S, Tanaka H, Watanabe T, Mizowaki T, Suzuki M. Quantitative autoradiography in boron neutron capture therapy considering the particle ranges in the samples. Phys Medica 2021;82:306–20. https://doi.org/10.1016/j.ejmp.2021.02.012.

PR4-3

[1] Fukusumi et al. (2018), Peer J, DOI 10.7717/peerj.4187

[2]S.Nakagawa et al. Cell Mol Neurobiol 27(2007) 687–694. DOI 10.1007/s10571-007-9195-4

[3] N. Kondo et al. Radiat. Environ. Biophys. 55 (2016) 89–94.

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