Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.
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.
Saga
T
T
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
Sakahara
H
H
Nakamoto
Y
Y
Sato
N
N
Ishimori
T
T
Mamede
M
M
Kobayashi
H
H
Masunaga
S
S
Sasai
K
K
Kuroki
M
M
Konishi
J
J
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
D002272:Carcinoembryonic Antigen; D007457:Iodine Radioisotopes