Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia

PMID: 11435076
Journal: European journal of cancer (Oxford, England : 1990) (volume: 37, issue: 11, Eur. J. Cancer 2001 Jul;37(11):1429-34)
Published: 2001-07-01

Authors:
Saga T, Sakahara H, Nakamoto Y, Sato N, Ishimori T, Mamede M, Kobayashi H, Masunaga S, Sasai K, Kuroki M, Konishi J

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.