title: Targeted concurrent chemoradiotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo.
abstract: OBJECTIVE
  The effect of alginate-hyaluronate microcapsules that release carboplatin in response to radiation was improved by adding ascorbic acid (AA).
  
  
  METHODS
  Four measures of the effectiveness of the microcapsules were evaluated: 1) release of carboplatin in response to radiation in vitro and in vivo; 2) detectability of their accumulation by computed tomography (CT) in vivo; 3) enhancement of antitumor effects in vivo; and 4) reduction of adverse effects in vivo.
  
  
  RESULTS
  There were significant increases in the rupture of microcapsules by adding AA in vitro. Subcutaneously injected microcapsules around the tumor could be detected by using CT and the alteration of CT-values correlated with the accumulation of the microcapsules. Those microcapsules released carboplatin and resulted in synergistic antitumor effect with concomitant radiation. With the encapsulation of carboplatin, chemotherapeutic effects were still observed two weeks after treatment. However, addition of AA did not result in increased antitumor effect in vivo. A reduction in adverse effects was observed with the encapsulation of carboplatin, through localization of carboplatin around the tumor.
  
  
  CONCLUSIONS
  Addition of AA to the materials of microcapsules did not result in increasing antitumor effect. However encapsulation of carboplatin will be useful as a clinical cancer-therapy option.
authors.affiliation: Department of Radiology, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505 Japan. Electronic address: sharada@iwate-med.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Harada
authors.affiliation: Department of Radiology, School of Medicine, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate, 020-8505 Japan. Electronic address: eharas@iwate-med.ac.jp.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Ehara
authors.affiliation: Department of Quantum Science and Energy Engineering, Tohoku University, 6-6 Aramaki, Aza Aoba, Sendai Miyagi, 980-8579 Japan. Electronic address: keizo.ishii@qse.tohoku.ac.jp.
authors.forename: Keizo
authors.initials: K
authors.lastname: Ishii
authors.affiliation: Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma, 370-1292 Japan. Electronic address: satoh.takahiro37@jaea.go.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma, 370-1292 Japan. Electronic address: koka.masashi@jaea.go.jp.
authors.forename: Masashi
authors.initials: M
authors.lastname: Koka
authors.affiliation: Takasaki Advanced Radiation Research Institute, Japan Atomic Energy Agency, 1233 Watanuki, Takasaki, Gunma, 370-1292 Japan. Electronic address: kamiya.tomihiro@jaea.go.jp.
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Kamiya
authors.affiliation: Cyclotron Center, Iwate Medical University, 348-58 Tomegamori, Takizawa, Iwate, 020-0173 Japan. Electronic address: ksera@iwate-med.ac.jp.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Sera
authors.affiliation: Nishina Memorial Cyclotron Center (NMCC), Japan Radioisotope Association, 348-58 Tomegamori, Takizawa, Iwate, 020-0173 Japan. Electronic address: goto@jrias.or.jp.
authors.forename: Shyoko
authors.initials: S
authors.lastname: Goto
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002214:Capsules / Q000008:administration & dosage* / Q000528:radiation effects; D016190:Carboplatin / Q000008:administration & dosage* / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000528:radiation effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000628:therapy*; D014057:Tomography, X-Ray Computed; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D016190:Carboplatin
keywords: Cancer therapy; Drug delivery system; Microcapsule; Radiation