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 rad iolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity o f the tumour were investigated. Nude mice bearing human colon cancer xenogr afts were heated to 40 degreesC for 3 or 6 h. After heating, mice received intravenous (i.v,) injections of [I-131]-labelled anti-carcinoembryonic ant igen (CEA) monoclonal antibody. Although 6-h heating did not alter the biod istribution of the radiolabelled antibody, and alone did not show any thera peutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also sig nificantly enhanced the effect of radio-immunotherapy. Co lony formation assay showed that the radiosensitivity of the tumour was sig nificantly 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-im munotherapy by increasing the radiosensitivity of the tumour. (C) 2001 Else vier Science Ltd. All rights reserved.