Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies

Jeffery A. Williams, Barry W. Wessels, Moody D. Wharam, Stanley E. Order, Philip M. Wanek, J. Kenneth Poggenburg, Jerry L. Klein

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Abstract

Radiolabeled antibodies provide a potential basis for selective radiotherapy of human gliomas. We have measured tumor targeting by radiolabeled monoclonal and polyclonal antibodies directed against neuroectodermal and tumor-associated antigens in nude mice bearing human glioma xenografts. Monoclonal P96.5, a mouse IgG2a immuno-globulin, defines an epitope of a human melanoma cell surface protein, and specifically binds the U-251 human glioma as measured by immunoperoxidase histochemistry. 111In-radiolabeled P96.5 specifically targets the U-251 human glioma xenograft and yields 87.0 microCuries (μCi) of tumor activity per gram per 100 μCi injected activity compared to 4.5 μCi following administration of radiolabeled irrelevant monoclonal antibody. Calculations of targeting ratios demonstrate deposited dose to be 11.6 times greater with radiolabeled P96.5 administration compared to irrelevant monoclonal antibody. The proportion of tumor dose found in normal organs is less than 10%, further supporting specific targeting of the human glioma xenograft by this antibody. Monoclonal antibody ZME018, which defines a second melanoma-associated antigen, and polyclonal rabbit antiferritin, which defines a tumor-associated antigen, demonstrate positive immunoperoxidase staining of the tumor, but comparatively decreased targeting. When compared to the 111In-radiolabeled antibody, 90Y-radiolabeled P96.5 demonstrates comparable tumor targeting and percentages of tumor dose found in normal organs. To test the therapeutic potential of 90Y-radiolabeled P96.5, tumors and normal sites were implanted with miniature thermoluminescent dosimeters (TLD). Seven days following administration of 100 μCi 90Y-radiolabeled P96.5, average absorbed doses of 3770, 980, 353, and 274 cGy were observed in tumor, liver, contralateral control site, and total body, respectively. Shared cell surface antigens among neuroectodermally derived neoplasms provide a basis for exploration of human glioma radioimmunotherapy.

Original languageEnglish (US)
Pages (from-to)1367-1375
Number of pages9
JournalInternational Journal of Radiation Oncology, Biology, Physics
Volume18
Issue number6
DOIs
Publication statusPublished - 1990

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Keywords

  • Human glioma
  • Radioimmunotherapy
  • Thermoluminescent dosimetry
  • Tumor localization

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

Williams, J. A., Wessels, B. W., Wharam, M. D., Order, S. E., Wanek, P. M., Poggenburg, J. K., & Klein, J. L. (1990). Targeting of human glioma xenografts in vivo utilizing radiolabeled antibodies. International Journal of Radiation Oncology, Biology, Physics, 18(6), 1367-1375. https://doi.org/10.1016/0360-3016(90)90310-G