Journal
EUROPEAN JOURNAL OF CANCER
Volume 37, Issue 11, Pages 1429-1434Publisher
ELSEVIER SCI LTD
DOI: 10.1016/S0959-8049(01)00138-1
Keywords
radio-immunotherapy; whole-body hyperthermia; radiolabelled monoclonal antibody; carcinoembryonic antigen; hypoxia
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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 degreesC for 3 or 6 h. After heating, mice received intravenous (i.v,) injections of [(131)I]-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 sig nificantly 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. (C) 2001 Elsevier Science Ltd. All rights reserved.
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