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Sequential Radioimmunotherapy with (177)Lu- and (211)At-Labeled Monoclonal Antibody BR96 in a Syngeneic Rat Colon Carcinoma Model.

Eriksson, Sophie LU ; Elgström, Erika LU ; Bäck, Tom; Ohlsson, Tomas G LU ; Jensen, Holger; Nilsson, Rune LU ; Lindegren, Sture and Tennvall, Jan LU (2014) In Cancer Biotherapy & Radiopharmaceuticals 29(6). p.238-246
Abstract
Abstract Alpha-particle emitters, such as astatine-211 ((211)At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 ((177)Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body... (More)
Abstract Alpha-particle emitters, such as astatine-211 ((211)At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 ((177)Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of (211)At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any (211)At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Results: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with (211)At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of (177)Lu-BR96 and (211)At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Cancer Biotherapy & Radiopharmaceuticals
volume
29
issue
6
pages
238 - 246
publisher
Mary Ann Liebert, Inc.
external identifiers
  • pmid:24971673
  • wos:000339910500002
  • scopus:84904631605
ISSN
1557-8852
DOI
10.1089/cbr.2014.1625
language
English
LU publication?
yes
id
82848f80-b339-48c7-9bcf-4d3e5bd07fbd (old id 4526660)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24971673?dopt=Abstract
date added to LUP
2014-07-08 11:14:26
date last changed
2017-01-01 03:12:33
@article{82848f80-b339-48c7-9bcf-4d3e5bd07fbd,
  abstract     = {Abstract Alpha-particle emitters, such as astatine-211 ((211)At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 ((177)Lu), have a longer path length and are considered better for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a (177)Lu-labeled antibody, followed by a (211)At-labeled antibody 25 days later. Methods: Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight (177)Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of (211)At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any (211)At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Results: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with (211)At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Conclusions: Sequential administration of (177)Lu-BR96 and (211)At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.},
  author       = {Eriksson, Sophie and Elgström, Erika and Bäck, Tom and Ohlsson, Tomas G and Jensen, Holger and Nilsson, Rune and Lindegren, Sture and Tennvall, Jan},
  issn         = {1557-8852},
  language     = {eng},
  number       = {6},
  pages        = {238--246},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Cancer Biotherapy & Radiopharmaceuticals},
  title        = {Sequential Radioimmunotherapy with (177)Lu- and (211)At-Labeled Monoclonal Antibody BR96 in a Syngeneic Rat Colon Carcinoma Model.},
  url          = {http://dx.doi.org/10.1089/cbr.2014.1625},
  volume       = {29},
  year         = {2014},
}