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Radionuclide-antibody conjugates for single-cell cytotoxicity
Article first published online: 12 FEB 2002
Copyright © 2002 American Cancer Society
Supplement: Eighth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer
Volume 94, Issue Supplement 4, pages 1215–1223, 15 February 2002
How to Cite
Mattes, M. J. (2002), Radionuclide-antibody conjugates for single-cell cytotoxicity. Cancer, 94: 1215–1223. doi: 10.1002/cncr.10288
- Issue published online: 12 FEB 2002
- Article first published online: 12 FEB 2002
- Manuscript Accepted: 14 NOV 2001
- Manuscript Received: 31 OCT 2001
- U.S. Public Health Service. Grant Number: CA87059
- National Institutes of Health
- radiolabeled antibodies;
- antibody-mediated cytotoxicity;
- Auger electron emitters
Radioimmunotherapy has primarily utilized high-energy β-particles, which are intended to kill macroscopic tumor masses. Such conjugates do not kill single cells or micrometastases efficiently. For killing single cells, it may be preferable to use radiation with a much shorter path length, such as α-particles or Auger or conversion electrons.
This selective review focuses on the use of radiolabeled antibody (Ab) conjugates to achieve single-cell kill. The advantages and disadvantages of particular types of radionuclides, the significance of intracellular localization of the Ab, and the potential clinical application of this approach are discussed. Potentially useful radionuclides are listed.
Auger and conversion electrons can kill cells effectively, with at least 6 logs of cell kill. Abs on the cell surface are only slightly less potent than Abs internalized into the cytoplasm, and this is consistent with theoretical considerations. α-Particles kill single cells very effectively, but the short half-lives of the available α-particle emitters are probably a disadvantage. High-energy β-particles can also kill single cells if they bind in sufficient amounts, but their disadvantage appears to be greater nonspecific toxicity.
Single-cell kill can be obtained with radionuclide-Ab conjugates. The selection of the optimal radionuclide may depend on the details of the clinical situation, such as the size and accessibility of the tumor burden, and the particular Ab to be used. Direct comparisons of various radionuclides are required in order to identify the optimal approach. However, for single-cell kill, as required for therapy of micrometastases, the use of Auger and conversion electron emitters appears to have substantial advantages. While current methods limit the applicability of this approach to Abs having a high level of binding, it may be applicable to lower-density antigens if higher specific activities or more potent radionuclides can be used. Tumor cure may require a mixture of radionuclides intended to kill both single cells and large tumor masses. Cancer 2002;94:1215–23. © 2002 American Cancer Society.