High-Dose Radioimmunotherapy Combined With Extracorporeal Depletion in a Syngeneic Rat Tumor Model
(2010) In Cancer 116(4). p.1043-1052- Abstract
- BACKGROUND: 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. METHODS: Rats were injected with high activities/body weight of lutetium (Lu-177)- or yttrium (Y-90)-labeled antibody conjugates (monoclonal antibody tetraazacyclododecanetetraacetic acid-biotin) and subjected to removal of the conjugate from the circulation by extracorporeal affinity adsorption treatment... (More)
- BACKGROUND: 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. METHODS: Rats were injected with high activities/body weight of lutetium (Lu-177)- or yttrium (Y-90)-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. RESULTS: The MTD of Lu-177- or Y-90-labeled immunoconjugates could be increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with Lu-177- or Y-90-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 x 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection. CONCLUSIONS: 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 beta-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease. (C) 2010 American Cancer Society. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1571129
- author
- Mårtensson, Linda LU ; Nilsson, Rune LU ; Ohlsson, Tomas G LU ; Sjögren, Hans Olof LU ; Strand, Sven-Erik LU and Tennvall, Jan LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- syngeneic tumor model, carcinoma, radioimmunotherapy, antibody, radionuclide therapy
- in
- Cancer
- volume
- 116
- issue
- 4
- pages
- 1043 - 1052
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- wos:000274316000006
- scopus:76249129905
- pmid:20127949
- ISSN
- 1097-0142
- DOI
- 10.1002/cncr.24791
- language
- English
- LU publication?
- yes
- id
- b92f2ae8-0866-4f92-9e2c-798978a92649 (old id 1571129)
- date added to LUP
- 2016-04-01 10:30:54
- date last changed
- 2022-01-25 23:59:52
@article{b92f2ae8-0866-4f92-9e2c-798978a92649,
abstract = {{BACKGROUND: 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. METHODS: Rats were injected with high activities/body weight of lutetium (Lu-177)- or yttrium (Y-90)-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. RESULTS: The MTD of Lu-177- or Y-90-labeled immunoconjugates could be increased 2.0x or 1.5x, respectively, when RIT was combined with extracorporeal affinity adsorption treatment. All animals treated with Lu-177- or Y-90-labeled antibodies showed persistent complete response of manifest tumors (approximately 10 x 15 mm) within 16 days postinjection. However, several animals showed disseminated disease 1.5 to 3 months postinjection. CONCLUSIONS: 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 beta-emitting radionuclides seems not to be effective in microscopic disease, because metastases developed at sites without previously known disease. (C) 2010 American Cancer Society.}},
author = {{Mårtensson, Linda and Nilsson, Rune and Ohlsson, Tomas G and Sjögren, Hans Olof and Strand, Sven-Erik and Tennvall, Jan}},
issn = {{1097-0142}},
keywords = {{syngeneic tumor model; carcinoma; radioimmunotherapy; antibody; radionuclide therapy}},
language = {{eng}},
number = {{4}},
pages = {{1043--1052}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Cancer}},
title = {{High-Dose Radioimmunotherapy Combined With Extracorporeal Depletion in a Syngeneic Rat Tumor Model}},
url = {{http://dx.doi.org/10.1002/cncr.24791}},
doi = {{10.1002/cncr.24791}},
volume = {{116}},
year = {{2010}},
}