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Repeated Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.

Eriksson, Sophie LU ; Ohlsson, Tomas G LU ; Nilsson, Rune LU and Tennvall, Jan LU (2012) In Cancer Biotherapy & Radiopharmaceuticals 27(2). p.134-140
Abstract
Abstract Aim: Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration. Methods: Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the... (More)
Abstract Aim: Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration. Methods: Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the maximal tolerated dose. Results: The additional treatment resulted in tolerable myelotoxicity; however, the frequency of metastatic disease and survival were not affected. Immunohistochemistry demonstrated binding of the BR96 antibody to tissue sections of analyzed metastases. Conclusions: In our model, development of metastatic disease after treatment of the manifest tumor was not prevented by an additional treatment with the same radioimmunoconjugate. Therefore, the antibody should be labeled with a more suitable radionuclide for treatment of metastases. The repeated targeted therapy was well tolerated in aspects of myelotoxicity. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
metastases, radioimmunotherapy, Lutetium-177, colon carcinoma, fractionation
in
Cancer Biotherapy & Radiopharmaceuticals
volume
27
issue
2
pages
134 - 140
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000301440900005
  • pmid:22229635
  • scopus:84858432399
ISSN
1557-8852
DOI
10.1089/cbr.2011.1080
language
English
LU publication?
yes
id
a91e0d76-6e9c-462e-9341-32fca6bc2ed8 (old id 2336600)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22229635?dopt=Abstract
date added to LUP
2012-02-01 20:12:50
date last changed
2017-06-25 03:58:10
@article{a91e0d76-6e9c-462e-9341-32fca6bc2ed8,
  abstract     = {Abstract Aim: Fractionation is generally used as a mean to improve radioimmunotherapy (RIT). Since RIT is considered suitable for small-volume disease, the aim of the current study was to investigate whether repeated administration of (177)Lu-labeled mAb BR96 was tolerated and could delay or prevent metastatic disease after complete remission of the tumor obtained by the first administration. Methods: Immunocompetent rats bearing a syngeneic colon carcinoma were first treated with 400 MBq/kg (177)Lu-DOTA-BR96, an activity resulting in complete response in 29 of 30 animals. On day 21, two groups of rats were given an additional activity of 150 or 350 MBq/kg resulting in total administered activities corresponding to 0.9 and 1.3 times the maximal tolerated dose. Results: The additional treatment resulted in tolerable myelotoxicity; however, the frequency of metastatic disease and survival were not affected. Immunohistochemistry demonstrated binding of the BR96 antibody to tissue sections of analyzed metastases. Conclusions: In our model, development of metastatic disease after treatment of the manifest tumor was not prevented by an additional treatment with the same radioimmunoconjugate. Therefore, the antibody should be labeled with a more suitable radionuclide for treatment of metastases. The repeated targeted therapy was well tolerated in aspects of myelotoxicity.},
  author       = {Eriksson, Sophie and Ohlsson, Tomas G and Nilsson, Rune and Tennvall, Jan},
  issn         = {1557-8852},
  keyword      = {metastases,radioimmunotherapy,Lutetium-177,colon carcinoma,fractionation},
  language     = {eng},
  number       = {2},
  pages        = {134--140},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Cancer Biotherapy & Radiopharmaceuticals},
  title        = {Repeated Radioimmunotherapy with (177)Lu-DOTA-BR96 in a Syngeneic Rat Colon Carcinoma Model.},
  url          = {http://dx.doi.org/10.1089/cbr.2011.1080},
  volume       = {27},
  year         = {2012},
}