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High-dose radioimmunotherapy combined with extracorporeal depletion in a syngeneic rat tumor model†
Evaluation of toxicity, therapeutic effect, and tumor model
Article first published online: 2 FEB 2010
Copyright © 2010 American Cancer Society
Supplement: Cancer Therapy With Antibodies and Immunoconjugates, Supplement to Cancer
Volume 116, Issue Supplement 4, pages 1043–1052, 15 February 2010
How to Cite
Mårtensson, L., Nilsson, R., Ohlsson, T., Sjögren, H.-O., Strand, S.-E. and Tennvall, J. (2010), High-dose radioimmunotherapy combined with extracorporeal depletion in a syngeneic rat tumor model. Cancer, 116: 1043–1052. doi: 10.1002/cncr.24791
The articles in this supplement were presented at the “12th Conference on Cancer Therapy With Antibodies and Immunoconjugates,” Parsippany, New Jersey, October 16-18, 2008.
- Issue published online: 2 FEB 2010
- Article first published online: 2 FEB 2010
- Manuscript Accepted: 21 OCT 2009
- Manuscript Received: 10 JUL 2009
- radionuclide therapy;
- syngeneic tumor model
The aim of the current study was to investigate the possibility of increasing the maximal tolerated dose (MTD) of a tumor-selective radiolabeled antibody when radioimmunotherapy (RIT) is combined with extracorporeal depletion of radioimmunoconjugates from the circulation. Furthermore, the authors evaluated whether this increase in dose improved the therapeutic effect on solid manifest tumors in an immunocompetent animal model.
Rats were injected with high activities/body weight of lutetium (177Lu)- or yttrium (90Y)-labeled antibody conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment 24 hours postinjection. Myelotoxicity was assessed by analysis of blood parameters for 12 weeks. The effect of increased doses in combination with extracorporeal affinity adsorption treatment was evaluated with respect to myelotoxicity and therapeutic effect in a syngeneic rat colon cancer model.
The MTD of 177Lu- or 90Y-labeled immunoconjugates could be increased 2.0× or 1.5×, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with 177Lu- or 90Y-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 × 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection.
Extracorporeal affinity adsorption treatment is a method that safely and efficiently reduces myelotoxicity associated with RIT. Extracorporeal affinity adsorption treatment allows increased administered activity without increased toxicity, with the aim of increasing the absorbed dose to the tumor. However, because tumor/normal tissue radiosensitivity ratios are more favorable in rodents, it is not possible to draw any conclusions concerning the therapeutic efficacy of increased administered activity in combination with extracorporeal affinity adsorption treatment in this study. Targeted RIT with β-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease. Cancer 2010;116(4 suppl):1043–52. © 2010 American Cancer Society.