Therapeutic Efficacy and Radiobiological Effects of Boric Acid-mediated BNCT in a VX2 Multifocal Liver Tumor-bearing Rabbit Model

Yi-Hsuan Hung; Yu-Chuan Lin; Yu-Ting Lin; Guan-Wen Shih; Jiunn-Wang Liao; Kuan-Sheng Chen; Hong-Ming Liu; Yi-Wei Chen; Yung-Jen Chuang; Chia-Min Yang; Jinn-Jer Peir; Chin-Hua Yang; Fong-In Chou

doi:10.21873/anticanres.13742

Therapeutic Efficacy and Radiobiological Effects of Boric Acid-mediated BNCT in a VX2 Multifocal Liver Tumor-bearing Rabbit Model

Anticancer Res. 2019 Oct;39(10):5495-5504. doi: 10.21873/anticanres.13742.

Authors

Yi-Hsuan Hung¹, Yu-Chuan Lin², Yu-Ting Lin², Guan-Wen Shih¹, Jiunn-Wang Liao³, Kuan-Sheng Chen^{4

5}, Hong-Ming Liu², Yi-Wei Chen⁶, Yung-Jen Chuang^{7

8}, Chia-Min Yang⁹, Jinn-Jer Peir², Chin-Hua Yang^{10

11}, Fong-In Chou^{12

2}

Affiliations

¹ Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
² Nuclear Science and Technology Development Center, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
³ Graduate Institute of Veterinary Pathobiology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, R.O.C.
⁴ Veterinary Medical Teaching Hospital, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, R.O.C.
⁵ Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan, R.O.C.
⁶ Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
⁷ Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
⁸ Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
⁹ Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
¹⁰ Department of Medical Imaging, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan, R.O.C.
¹¹ Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, R.O.C.
¹² Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu, Taiwan, R.O.C. fichou@mx.nthu.edu.tw.

PMID: 31570443
DOI: 10.21873/anticanres.13742

Abstract

Background/aim: Most patients with hepatocellular carcinoma (HCC) cannot be treated using traditional therapies. Boron neutron capture therapy (BNCT) may provide a new treatment for HCC. In this study, the therapeutic efficacy and radiobiological effects of boric acid (BA)-mediated BNCT in a VX2 multifocal liver tumor-bearing rabbit model are investigated.

Materials and methods: Rabbits were irradiated with neutrons at the Tsing Hua Open Pool Reactor 35 min following an intravenous injection of BA (50 mg ¹⁰B/kg BW). The tumor size following BNCT treatment was determined by ultrasonography. The radiobiological effects were identified by histopathological examination.

Results: A total of 92.85% of the tumors became undetectable in the rabbits after two fractions of BNCT treatment. The tumor cells were selectively eliminated and the tumor vasculature was collapsed and destroyed after two fractions of BA-mediated BNCT, and no injury to the hepatocytes or blood vessels was observed in the adjacent normal liver regions.

Conclusion: Liver tumors can be cured by BA-mediated BNCT in the rabbit model of a VX2 multifocal liver tumor. BA-mediated BNCT may be a breakthrough therapy for hepatocellular carcinoma.

Keywords: Boric acid; boron neutron capture therapy (BNCT); hepatocellular carcinoma; multifocal liver tumor; rabbit model; radiobiological effects; therapeutic efficacy.

MeSH terms

Animals
Blood Vessels / drug effects
Blood Vessels / radiation effects
Boric Acids / pharmacology*
Boron Neutron Capture Therapy / methods
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / radiotherapy*
Hepatocytes / drug effects
Hepatocytes / radiation effects
Liver / drug effects
Liver / radiation effects
Liver Neoplasms / drug therapy*
Liver Neoplasms / radiotherapy*
Male
Rabbits

Substances

Boric Acids
boric acid