The purpose of this study was to investigate the effects of tumor-localized hyperthermia at 42°C on the tissue distribution of radioiodinated monoclonal antibody F(ab′)2 fragments. Paired-label biodistribution measurements were performed in athymic mice bearing D-54 MG human glioma xenografts on one leg. Mice received both the 131I-labeled F(ab′)2 fragment of Mel-14, reactive with human gliomas and melanomas, and nonspecific 125I-labeled RPC 5 F(ab′)2. Tumor-bearing legs were placed in a 42°C water bath or a 37°C water bath (control) for 2 or 4 h. In mice sacrificed immediately after 2 h of heating, no hyperthermia-induced differences in the distribution of either fragment were observed. In the 4-h groups, tumor uptake of Mel-14 F(ab′)2 increased from 7.04 ± 1.59% injected dose (ID)/g at 37°C to 20.65 ± 4.53% ID/g at 42°C (P < 0.0001), and tumor localization of the control fragment rose from 5.23 ± 1.35% ID/g to 14.51 ± 1.37% ID/g (P < 0.0001). In another experiment, F(ab′)2 fragments were injected, tumors were heated for 4 h, and groups were sacrificed at 4, 8, and 16 h after injection. Statistically significant 2- to 3-fold higher uptake of both fragments in tumor were observed at all time points. Hyperthermic conditions also resulted in higher tumor:tissue ratios for both fragments. These results suggest that it may be possible to use tumor-localized hyperthermia to increase the therapeutic utility of radiolabeled monoclonal antibodies, particularly when labeled with short lived nuclides such as the 7.2-h α-emitter 211At.

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Supported by DOE Grant DEFG05-89ER60789, and NIH Grants CA 42324, CA 20023, CA 44630, NS00958, CA 11898, CA 42745, and CA 40355.

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