Single-dose toxicity study by intra-arterial injection of 10BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma

Hironobu Yanagie; Masashi Yanagawa; Tsuyoshi Higuchi; Ryouji Mizumachi; Mitsuteru Fujihara; Yasuyuki Morishita; Yuriko Sakurai; Kikue Mouri; Novriana Dewi; Yasumasa Nonaka; Atsuko Shinohara; Takehisa Matsukawa; Ayano Kubota; Kazuhito Yokoyama; Minoru Suzuki; Shin-Ichiro Masunaga; Yohinori Sakurai; Hiroki Tanaka; Koji Ono; Haruo Yamauchi; Minoru Ono; Jun Nakajima; Shushi Higashi; Hiroyuki Takahashi

doi:10.1016/j.apradiso.2020.109202

Single-dose toxicity study by intra-arterial injection of ¹⁰BSH entrapped water-in-oil-in-water emulsion for boron neutron capture therapy to hepatocellular carcinoma

Appl Radiat Isot. 2020 Sep:163:109202. doi: 10.1016/j.apradiso.2020.109202. Epub 2020 May 13.

Authors

Hironobu Yanagie¹, Masashi Yanagawa², Tsuyoshi Higuchi³, Ryouji Mizumachi³, Mitsuteru Fujihara⁴, Yasuyuki Morishita⁵, Yuriko Sakurai⁶, Kikue Mouri⁶, Novriana Dewi⁶, Yasumasa Nonaka⁷, Atsuko Shinohara⁸, Takehisa Matsukawa⁹, Ayano Kubota⁹, Kazuhito Yokoyama⁹, Minoru Suzuki¹⁰, Shin-Ichiro Masunaga¹⁰, Yohinori Sakurai¹⁰, Hiroki Tanaka¹⁰, Koji Ono¹¹, Haruo Yamauchi¹², Minoru Ono¹², Jun Nakajima¹³, Shushi Higashi¹⁴, Hiroyuki Takahashi¹⁵

Affiliations

¹ Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, 113-8656, Japan; Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan; Research Institute of Healthy Living, Niigata University of Pharmacy & Applied Life Sciences, Niigata, 956-8603, Japan. Electronic address: yanagie@n.t.u-tokyo.ac.jp.
² Veterinary Medical Center, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, 080-8555, Japan.
³ Department of Pharmacology, Kumamoto Institute Branch, LSI Medience Ltd. Co., Kumamoto, 869-0425, Japan.
⁴ SPG Techno Ltd. Co., Miyazaki, 880-0303, Japan.
⁵ Department of Human & Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-8655, Japan.
⁶ Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan; Research Institute of Healthy Living, Niigata University of Pharmacy & Applied Life Sciences, Niigata, 956-8603, Japan.
⁷ Department of Surgery, Keiai-kai Hoyo Hospital, Iwate, 028-3111, Japan.
⁸ Department of Humanities, The Graduate School of Seisen University, Tokyo, 141-8642, Japan; Department of Hygiene, Faculty of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
⁹ Department of Hygiene, Faculty of Medicine, Juntendo University, Tokyo, 113-8421, Japan.
¹⁰ Kyoto Univ Institute for Integrated Radiation & Nuclear Science, Osaka, 590-0494, Japan.
¹¹ Kansai BNCT Medical Center, Osaka Medical College, Osaka, 569-8686, Japan.
¹² Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan; Department of Cardiac Surgery, The University of Tokyo Hospital, Tokyo, 113-8655, Japan.
¹³ Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan; Department of Pulmonary Surgery, The University of Tokyo Hospital, Tokyo, 113-8655, Japan.
¹⁴ Department of Surgery, Kojin-kai Medicalcity East Hospital, Miyazaki, 885-0035, Japan.
¹⁵ Institute of Engineering Innovation, School of Engineering, The University of Tokyo, Tokyo, 113-8656, Japan; Cooperative Unit of Medicine & Engineering, The University of Tokyo Hospital, Tokyo, 113-8655, Japan.

PMID: 32561043
DOI: 10.1016/j.apradiso.2020.109202

Abstract

We developed a mixing medical device by attaching Shirasu porous glass Millipore membrane to prepare water-in-oil-in-water (WOW) emulsion in a shorter time to be applied as ¹⁰B-entrapped WOW emulsion for hepatocellular carcinoma (HCC) treatment. Single-dose toxicity studies by intra-arterial injection of ¹⁰BSH-entrapped WOW were performed in rabbits and pig, and no side effects were observed. We hope to proceed to the preclinical and clinical studies for further evaluation of ¹⁰B compound as multidisciplinary treatments for HCC.

Keywords: BNCT; Hepatocellular carcinoma; Intra-arterial injection; Mixing medical device; WOW emulsion.

MeSH terms

Animals
Boron Compounds / administration & dosage
Boron Compounds / toxicity*
Boron Neutron Capture Therapy / methods*
Carcinoma, Hepatocellular / radiotherapy*
Emulsions
Injections, Intra-Arterial
Liver Neoplasms / radiotherapy*
Oils
Rabbits
Swine
Water

Substances

Boron Compounds
Emulsions
Oils
Water