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Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia.

Publication ,  Journal Article
Cope, DA; Dewhirst, MW; Friedman, HS; Bigner, DD; Zalutsky, MR
Published in: Cancer Res
March 15, 1990

The purpose of this study was to investigate the effects of tumor-localized hyperthermia at 42 degrees 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 degrees C water bath or a 37 degrees 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 degrees C to 20.65 +/- 4.53% ID/g at 42 degrees C (P less than 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 less than 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 alpha-emitter 211At.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 15, 1990

Volume

50

Issue

6

Start / End Page

1803 / 1809

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Distribution
  • Radioisotope Dilution Technique
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • Male
  • Iodine Radioisotopes
  • Immunoglobulin G
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cope, D. A., Dewhirst, M. W., Friedman, H. S., Bigner, D. D., & Zalutsky, M. R. (1990). Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia. Cancer Res, 50(6), 1803–1809.
Cope, D. A., M. W. Dewhirst, H. S. Friedman, D. D. Bigner, and M. R. Zalutsky. “Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia.Cancer Res 50, no. 6 (March 15, 1990): 1803–9.
Cope DA, Dewhirst MW, Friedman HS, Bigner DD, Zalutsky MR. Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia. Cancer Res. 1990 Mar 15;50(6):1803–9.
Cope DA, Dewhirst MW, Friedman HS, Bigner DD, Zalutsky MR. Enhanced delivery of a monoclonal antibody F(ab')2 fragment to subcutaneous human glioma xenografts using local hyperthermia. Cancer Res. 1990 Mar 15;50(6):1803–1809.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 15, 1990

Volume

50

Issue

6

Start / End Page

1803 / 1809

Location

United States

Related Subject Headings

  • Transplantation, Heterologous
  • Tissue Distribution
  • Radioisotope Dilution Technique
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
  • Male
  • Iodine Radioisotopes
  • Immunoglobulin G