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Local Hyperthermia and SR 4233 Enhance the Antitumor Effects of Radioimmunotherapy in Nude Mice with Human Colonic Adenocarcinoma Xenografts

Local Hyperthermia and SR 4233 Enhance the Antitumor Effects of Radioimmunotherapy in Nude Mice... Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 ± 47 mm 3 (mean ± SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3. A single injection of 25 µCi 90 Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90 Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5°C for 1 h immediately following the injection of 111 In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% ( P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.07). The administration of local hyperthermia at 43.0°C for 1 h, on the other hand, had direct cytotoxic effects ( P = 0.03) and enhanced the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0°C and SR 4233 were administered in combination with 90 Y-NR-Lu-10 ( P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90 Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss. 1 Supported in part by an American Society for Therapeutic Radiology and Oncology Fellowship, a stipend from the Robert D. Plageman Memorial Fund, an American Cancer Society Career Development Award, NIH Research Grant CA 56464, and a gift from The Friends of Radiology. 2 To whom requests for reprints should be addressed, at Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Research American Association of Cancer Research

Local Hyperthermia and SR 4233 Enhance the Antitumor Effects of Radioimmunotherapy in Nude Mice with Human Colonic Adenocarcinoma Xenografts

Local Hyperthermia and SR 4233 Enhance the Antitumor Effects of Radioimmunotherapy in Nude Mice with Human Colonic Adenocarcinoma Xenografts

Cancer Research , Volume 53 (13): 3022 – Jul 1, 1993

Abstract

Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 ± 47 mm 3 (mean ± SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3. A single injection of 25 µCi 90 Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90 Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5°C for 1 h immediately following the injection of 111 In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% ( P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.07). The administration of local hyperthermia at 43.0°C for 1 h, on the other hand, had direct cytotoxic effects ( P = 0.03) and enhanced the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0°C and SR 4233 were administered in combination with 90 Y-NR-Lu-10 ( P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90 Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss. 1 Supported in part by an American Society for Therapeutic Radiology and Oncology Fellowship, a stipend from the Robert D. Plageman Memorial Fund, an American Cancer Society Career Development Award, NIH Research Grant CA 56464, and a gift from The Friends of Radiology. 2 To whom requests for reprints should be addressed, at Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305.

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Publisher
American Association of Cancer Research
Copyright
Copyright © 1993 by the American Association for Cancer Research.
ISSN
0008-5472
Publisher site

Abstract

Local hyperthermia and the hypoxic cytotoxin SR 4233 were administered to nude mice with 693 ± 47 mm 3 (mean ± SE) s.c. HCT-8 human colonic adenocarcinoma xenografts in an attempt to enhance the antitumor effects of radioimmunotherapy. Biodistribution studies revealed preferential binding of NR-Lu-10, a murine monoclonal antibody, to the tumors compared with an isotype-matched control antibody, CCOO16-3. A single injection of 25 µCi 90 Y-NR-Lu-10 significantly inhibited tumor growth (control versus 90 Y-NR-Lu-10: P = 0.048). The administration of hyperthermia at 41.5°C for 1 h immediately following the injection of 111 In-labeled NR-Lu-10 up-regulated tumor-associated antigen expression and increased antibody uptake in the tumors by 73% ( P = 0.001) without significantly affecting antibody uptake in normal tissues. However, the heat treatment did not produce a more homogeneous distribution of the antibodies in the tumors and did not significantly enhance the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.07). The administration of local hyperthermia at 43.0°C for 1 h, on the other hand, had direct cytotoxic effects ( P = 0.03) and enhanced the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.01). SR 4233 also enhanced the tumor growth delay produced by 90 Y-NR-Lu-10 ( P = 0.03). The greatest antitumor effects were observed when both hyperthermia at 43.0°C and SR 4233 were administered in combination with 90 Y-NR-Lu-10 ( P = 0.002). No toxicity was produced by the local hyperthermia, and the only toxicities produced by 90 Y-NR-Lu-10 and SR 4233 were neutropenia and weight loss. 1 Supported in part by an American Society for Therapeutic Radiology and Oncology Fellowship, a stipend from the Robert D. Plageman Memorial Fund, an American Cancer Society Career Development Award, NIH Research Grant CA 56464, and a gift from The Friends of Radiology. 2 To whom requests for reprints should be addressed, at Department of Radiation Oncology, Stanford University Medical Center, Stanford, CA 94305.

Journal

Cancer ResearchAmerican Association of Cancer Research

Published: Jul 1, 1993

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