title: Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.
abstract: To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.
authors: Department of Nuclear Medicine and Diagnostic Imaging, Graduate School of Medicine, Kyoto University, 54 Kawahara-cho, Shogoin, Sakyo-ku, 606-8507, Kyoto, Japan. saga@kuhp.kyoto-u.ac.jp
authors: T
authors: T
authors: Saga
authors: H
authors: H
authors: Sakahara
authors: Y
authors: Y
authors: Nakamoto
authors: N
authors: N
authors: Sato
authors: T
authors: T
authors: Ishimori
authors: M
authors: M
authors: Mamede
authors: H
authors: H
authors: Kobayashi
authors: S
authors: S
authors: Masunaga
authors: K
authors: K
authors: Sasai
authors: M
authors: M
authors: Kuroki
authors: J
authors: J
authors: Konishi
mesh_terms: D000818:Animals; D002272:Carcinoembryonic Antigen / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000628:therapy*; D003131:Combined Modality Therapy / Q000379:methods; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D016499:Radioimmunotherapy / Q000379:methods*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes