title: Synthesis and biological evaluation of new BSH-conjugated chlorin derivatives as agents for both photodynamic therapy and boron neutron capture therapy of cancer.
abstract: New disodium mercaptoundecahydro-closo-dodecaborate (BSH)-conjugated chlorin derivatives 11, 12, 16 and 20 as agents for both photodynamic therapy (PDT) and boron neutron capture therapy (BNCT) of cancer were synthesized. The in vivo biodistribution and clearance of 11, 12, 16 and 20 were investigated in tumor-bearing mice. Compounds 12 and 16 showed good tumor-selective accumulation among the four derivatives. The time to maximum accumulation of compound 16 in tumor tissue was one-fourth of that of compound 12, and clearance from normal tissues of compound 16 was similar to that of compound 12. The in vivo therapeutic efficacy of PDT using 16, which has twice as many boron atoms as 12, was evaluated by measuring tumor growth rates in tumor-bearing mice with 660 nm light-emitting diode irradiation at 6h after injection of 16. Tumor growth was significantly inhibited by PDT using 16. These results suggested that 16 is a good candidate for both PDT and BNCT of cancer.
authors.affiliation: Fushimi Pharmaceutical Co., Ltd., 1676 Nakazu-cho, Marugame, Kagawa 763-8605, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Asano
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Amon
authors.initials: A
authors.lastname: Nagami
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fukumoto
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Miura
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan.
authors.forename: Futoshi
authors.initials: F
authors.lastname: Yazama
authors.affiliation: Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Ito
authors.affiliation: Porphyrin Lab., 1-2-35 Tsushimanishizaka, Kita-ku, Okayama 700-0086, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Sakata
authors.affiliation: Faculty of Life and Environmental Sciences, Prefectural University of Hiroshima, 562 Nanatsuka-cho, Shobara, Hiroshima 727-0023, Japan. Electronic address: atai@pu-hiroshima.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tai
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000737:chemistry*; D016754:Boron Neutron Capture Therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D014184:Transplantation, Homologous
chemical_list: D001896:Boron Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; C119788:dodecaborate; C006969:chlorin
keywords: Boron neutron capture therapy; Chlorin derivatives; Photodynamic therapy; Porphyrin