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Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb

BACKGROUND: Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 ((211)At). Radioimmunotherapy utilizing α-particle emitting radionuclides is c...

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Autores principales: Eriksson, Sophie E, Bäck, Tom, Elgström, Erika, Jensen, Holger, Nilsson, Rune, Lindegren, Sture, Tennvall, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621254/
https://www.ncbi.nlm.nih.gov/pubmed/23557183
http://dx.doi.org/10.1186/2191-219X-3-23
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author Eriksson, Sophie E
Bäck, Tom
Elgström, Erika
Jensen, Holger
Nilsson, Rune
Lindegren, Sture
Tennvall, Jan
author_facet Eriksson, Sophie E
Bäck, Tom
Elgström, Erika
Jensen, Holger
Nilsson, Rune
Lindegren, Sture
Tennvall, Jan
author_sort Eriksson, Sophie E
collection PubMed
description BACKGROUND: Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 ((211)At). Radioimmunotherapy utilizing α-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a (211)At-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm. METHODS: Eighteen rats with subperitoneal syngeneic colon carcinoma were allocated to three groups of six animals together with three healthy rats in each group. The groups were injected intravenously with either 150 μg of unlabeled mAbs (controls) or 2.5 or 5 MBq (211)At-mAbs directed towards the Lewis Y antigen expressed on the cell membrane of several carcinomas. Tumor volume, body weight, and blood cell counts were monitored for 100 days after treatment. RESULTS: Local tumors were non-palpable in five out of six rats after treatment with both activities of (211)At-mAbs, compared to one out of six in the control group. At the study end, half of the animals in each group given (211)At-BR96 and one animal in the control group were free from disease. Radioimmunotherapy resulted in dose-dependent, transient weight loss and myelotoxicity. Survival was significantly better in the groups receiving targeted alpha therapy than in those receiving unlabeled mAbs. CONCLUSIONS: This study demonstrates the possibility of treating small, solid colon carcinoma tumors with α-emitting radionuclides such as (211)At bound to mAbs, with tolerable toxicity.
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spelling pubmed-36212542013-04-10 Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb Eriksson, Sophie E Bäck, Tom Elgström, Erika Jensen, Holger Nilsson, Rune Lindegren, Sture Tennvall, Jan EJNMMI Res Original Research BACKGROUND: Most carcinomas are prone to metastasize despite successful treatment of the primary tumor. One way to address this clinical challenge may be targeted therapy with α-emitting radionuclides such as astatine-211 ((211)At). Radioimmunotherapy utilizing α-particle emitting radionuclides is considered especially suitable for the treatment of small cell clusters and single cells, although lesions of different sizes may also be present in the patient. The aim of this study was primarily to evaluate the toxicity and secondarily in vivo efficacy of a (211)At-labeled monoclonal antibody (mAb) directed against colon carcinoma with tumor diameters of approximately 10 mm. METHODS: Eighteen rats with subperitoneal syngeneic colon carcinoma were allocated to three groups of six animals together with three healthy rats in each group. The groups were injected intravenously with either 150 μg of unlabeled mAbs (controls) or 2.5 or 5 MBq (211)At-mAbs directed towards the Lewis Y antigen expressed on the cell membrane of several carcinomas. Tumor volume, body weight, and blood cell counts were monitored for 100 days after treatment. RESULTS: Local tumors were non-palpable in five out of six rats after treatment with both activities of (211)At-mAbs, compared to one out of six in the control group. At the study end, half of the animals in each group given (211)At-BR96 and one animal in the control group were free from disease. Radioimmunotherapy resulted in dose-dependent, transient weight loss and myelotoxicity. Survival was significantly better in the groups receiving targeted alpha therapy than in those receiving unlabeled mAbs. CONCLUSIONS: This study demonstrates the possibility of treating small, solid colon carcinoma tumors with α-emitting radionuclides such as (211)At bound to mAbs, with tolerable toxicity. Springer 2013-04-04 /pmc/articles/PMC3621254/ /pubmed/23557183 http://dx.doi.org/10.1186/2191-219X-3-23 Text en Copyright ©2013 Eriksson et al.; licensee Springer. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Eriksson, Sophie E
Bäck, Tom
Elgström, Erika
Jensen, Holger
Nilsson, Rune
Lindegren, Sture
Tennvall, Jan
Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb
title Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb
title_full Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb
title_fullStr Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb
title_full_unstemmed Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb
title_short Successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)At-mAb
title_sort successful radioimmunotherapy of established syngeneic rat colon carcinoma with (211)at-mab
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621254/
https://www.ncbi.nlm.nih.gov/pubmed/23557183
http://dx.doi.org/10.1186/2191-219X-3-23
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