title: In vivo evaluation of neutron capture therapy effectivity using calcium phosphate-based nanoparticles as Gd-DTPA delivery agent.
abstract: OBJECTIVE
  A more immediate impact for therapeutic approaches of current clinical research efforts is of major interest, which might be obtained by developing a noninvasive radiation dose-escalation strategy, and neutron capture therapy represents one such novel approach. Furthermore, some recent researches on neutron capture therapy have focused on using gadolinium as an alternative or complementary for currently used boron, taking into account several advantages that gadolinium offers. Therefore, in this study, we carried out feasibility evaluation for both single and multiple injections of gadolinium-based MRI contrast agent incorporated in calcium phosphate nanoparticles as neutron capture therapy agent.
  
  
  METHODS
  In vivo evaluation was performed on colon carcinoma Col-26 tumor-bearing mice irradiated at nuclear reactor facility of Kyoto University Research Reactor Institute with average neutron fluence of 1.8 × 10(12) n/cm(2). Antitumor effectivity was evaluated based on tumor growth suppression assessed until 27 days after neutron irradiation, followed by histopathological analysis on tumor slice.
  
  
  RESULTS
  The experimental results showed that the tumor growth of irradiated mice injected beforehand with Gd-DTPA-incorporating calcium phosphate-based nanoparticles was suppressed up to four times higher compared to the non-treated group, supported by the results of histopathological analysis.
  
  
  CONCLUSIONS
  The results of antitumor effectivity observed on tumor-bearing mice after neutron irradiation indicated possible effectivity of gadolinium-based neutron capture therapy treatment.
authors.affiliation: Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Novriana
authors.initials: N
authors.lastname: Dewi
authors.affiliation: Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki, 212-0013, Japan.|Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan.|Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Peng
authors.initials: P
authors.lastname: Mi
authors.affiliation: Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. yanagie@my-pharm.ac.jp.|Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan. yanagie@my-pharm.ac.jp.|Department of Innovative Cancer Therapeutics: Alpha Particle and Immunotherapeutics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo, 204-8588, Japan. yanagie@my-pharm.ac.jp.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Yanagie
authors.affiliation: Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Department of Human and Molecular Pathology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morishita
authors.affiliation: Department of Applied Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2 Sen-11 Inadacho, Obihiro, Hokkaido, 080-0834, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagawa
authors.affiliation: Laboratory of Veterinary Surgery, Graduate School of Agricultural and Life Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Department of Humanities, Graduate School of Seisen University, 3-16-21 Higashi-Gotanda, Shinagawa-ku, Tokyo, 141-8642, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Shinohara
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Takehisa
authors.initials: T
authors.lastname: Matsukawa
authors.affiliation: Department of Epidemiology and Environmental Health, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yokoyama
authors.affiliation: Department of Bioengineering, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Horacio
authors.initials: H
authors.lastname: Cabral
authors.affiliation: Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Tanaka
authors.affiliation: Research Reactor Institute, Kyoto University, Asahiro nishi, Kumatori-cho, Sennan-gun, Osaka, 590-0494, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Ono
authors.affiliation: Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki, 212-0013, Japan.|Polymer Chemistry Division, Chemical Resources Laboratory, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nishiyama
authors.affiliation: Innovation Center of Nanomedicine, Kawasaki Institute of Industry Promotion, 66-20 Horikawa-cho, Saiwai-ku, Kawasaki, 212-0013, Japan.|Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.|Department of Materials Engineering, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kataoka
authors.affiliation: Department of Nuclear Engineering and Management, Graduate School of Engineering, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.|Cooperative Unit of Medicine and Engineering, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000008:administration & dosage*; D003110:Colonic Neoplasms / Q000473:pathology* / Q000532:radiotherapy*; D003287:Contrast Media / Q000008:administration & dosage*; D005240:Feasibility Studies; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage*; D006801:Humans; D007267:Injections; D007564:Japan; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage*; D009374:Neoplasms, Experimental / Q000532:radiotherapy; D017247:Neutron Capture Therapy / Q000379:methods*; D011879:Radiotherapy Dosage; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D002130:Calcium Phosphates; D003287:Contrast Media; C020243:calcium phosphate; D019786:Gadolinium DTPA
keywords: Calcium phosphate; Gadolinium; Nanoparticles; Neutron capture therapy