Folate-appended cyclodextrin improves the intratumoral accumulation of existing boron compounds

Yoshitaka Matsumoto; Kenjiro Hattori; Hidetoshi Arima; Keiichi Motoyama; Taishi Higashi; Hitoshi Ishikawa; Nobuyoshi Fukumitsu; Teruhito Aihara; Kei Nakai; Hiroaki Kumada; Hideyuki Sakurai

doi:10.1016/j.apradiso.2020.109201

Folate-appended cyclodextrin improves the intratumoral accumulation of existing boron compounds

Appl Radiat Isot. 2020 Sep:163:109201. doi: 10.1016/j.apradiso.2020.109201. Epub 2020 Apr 27.

Authors

Affiliations

¹ Radiation Oncology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Proton Medical Research Center, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan. Electronic address: ymatsumoto@pmrc.tsukuba.ac.jp.
² CyDing Co., Ltd., 5-1 Oe, Chuo-ku, Kumamoto, 862-0973, Japan.
³ Laboratory of Evidence-Based Pharmacotherapy, Daiichi University of Pharmacy, 22-1 Tamakawa, Minami-ku, Fukuoka, 815-8511, Japan.
⁴ Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
⁵ Priority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto, 862-0973, Japan.
⁶ Radiation Oncology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan; Proton Medical Research Center, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.
⁷ Department of Radiation Oncology, Kobe Proton Center, 1-6-8 Minatojima Minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
⁸ Faculty of Medicine, Osaka Medical College, 2-7 Daigakumachi, Takatsuki, Osaka, 569-8686, Japan.
⁹ Proton Medical Research Center, University of Tsukuba Hospital, 2-1-1 Amakubo, Tsukuba, Ibaraki, 305-8576, Japan.

PMID: 32561042
DOI: 10.1016/j.apradiso.2020.109201

Abstract

In this study, the tumor accumulation and antitumor effect of folate-modified cyclodextrin (ND201) purified with folate receptor (FR) connotated with BSH were examined. ND201 and BSH were stably bound in blood, and the mixing ratio 1:1 was most efficient. ND-BSH showed higher boron concentration (38.5 ppm) than BSH alone (11.25 ppm). The maximum ND-BSH tumor/blood ratio was also markedly higher (6.58) than that of BSH alone (1.04). ND-BSH showed a significant antitumor effect compared with BSH after neutron irradiation.

Keywords: BSH; Boron neutron capture therapy; Cyclodextrin; Folate receptor; iBNCT.

MeSH terms

Animals
Boron Compounds / blood
Boron Compounds / metabolism*
Boron Neutron Capture Therapy / methods
Cell Line, Tumor
Cyclodextrins / chemistry*
Folic Acid / chemistry*
Humans
Mice
Mice, Inbred BALB C
Neoplasms / metabolism*
Neoplasms / radiotherapy

Substances

Boron Compounds
Cyclodextrins
Folic Acid