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Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy

Mårtensson, Linda LU ; Nilsson, Rune; Ohlsson, Tomas G LU ; Sjögren, Hans Olof LU ; Strand, Sven-Erik LU and Tennvall, Jan LU (2007) In Clinical Cancer Research 13(18). p.5572-5576
Abstract
Purpose: Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT). Experimental Design: Rats were injected with biotinylated antibody and subjected to removal of the antibodies from the circulation by ECAT 24 h after injection (avidin column). Animals were then injected with In-111-1,4,7,10-tetra-azacylododecane N,N',N '',N'''-tetraacetic acid (DOTA) streptavidin. In a third step, animals were subjected to a second ECAT 8 h after injection to remove the DOTA-streptavidin from the circulation (biotin column). Biodistribution and tumor targeting of DOTA-streptavidin 24 h after injection was determined. Results: Elimination of biotinylated... (More)
Purpose: Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT). Experimental Design: Rats were injected with biotinylated antibody and subjected to removal of the antibodies from the circulation by ECAT 24 h after injection (avidin column). Animals were then injected with In-111-1,4,7,10-tetra-azacylododecane N,N',N '',N'''-tetraacetic acid (DOTA) streptavidin. In a third step, animals were subjected to a second ECAT 8 h after injection to remove the DOTA-streptavidin from the circulation (biotin column). Biodistribution and tumor targeting of DOTA-streptavidin 24 h after injection was determined. Results: Elimination of biotinylated antibody by ECAT before injection of DOTA-streptavidin increased the tumor targeting by 50%. In addition, the levels of DOTA-streptavidin in liver and lymph nodes were reduced by 60%, which implied a 4.3- and 3.8-fold increase of tumor-to-liver and tumor-to-lymph node ratios, respectively. By doing a second ECAT to remove DOTA-streptavidin from the circulation, accumulation in normal tissues was reduced. However, this latter ECAT also reduced tumor accumulation by 25% (mostly corresponding to radioactivity in the circulation). Conclusions: ECAT was efficient as a means of removing biotinylated antibodies and would probably also be efficient for the clearance of streptavidin-conjugated antibodies. Conversely, the use of ECAT for removal of radiolabeled streptavidin seems not to offer any advantage. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
13
issue
18
pages
5572 - 5576
publisher
American Association for Cancer Research
external identifiers
  • wos:000249889900011
  • scopus:34848917109
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-07-0891
language
English
LU publication?
yes
id
2d7c2666-85e3-4c20-865b-ff19585fdb2a (old id 686743)
date added to LUP
2007-12-13 13:11:31
date last changed
2017-01-01 04:46:27
@article{2d7c2666-85e3-4c20-865b-ff19585fdb2a,
  abstract     = {Purpose: Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT). Experimental Design: Rats were injected with biotinylated antibody and subjected to removal of the antibodies from the circulation by ECAT 24 h after injection (avidin column). Animals were then injected with In-111-1,4,7,10-tetra-azacylododecane N,N',N '',N'''-tetraacetic acid (DOTA) streptavidin. In a third step, animals were subjected to a second ECAT 8 h after injection to remove the DOTA-streptavidin from the circulation (biotin column). Biodistribution and tumor targeting of DOTA-streptavidin 24 h after injection was determined. Results: Elimination of biotinylated antibody by ECAT before injection of DOTA-streptavidin increased the tumor targeting by 50%. In addition, the levels of DOTA-streptavidin in liver and lymph nodes were reduced by 60%, which implied a 4.3- and 3.8-fold increase of tumor-to-liver and tumor-to-lymph node ratios, respectively. By doing a second ECAT to remove DOTA-streptavidin from the circulation, accumulation in normal tissues was reduced. However, this latter ECAT also reduced tumor accumulation by 25% (mostly corresponding to radioactivity in the circulation). Conclusions: ECAT was efficient as a means of removing biotinylated antibodies and would probably also be efficient for the clearance of streptavidin-conjugated antibodies. Conversely, the use of ECAT for removal of radiolabeled streptavidin seems not to offer any advantage.},
  author       = {Mårtensson, Linda and Nilsson, Rune and Ohlsson, Tomas G and Sjögren, Hans Olof and Strand, Sven-Erik and Tennvall, Jan},
  issn         = {1078-0432},
  language     = {eng},
  number       = {18},
  pages        = {5572--5576},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-07-0891},
  volume       = {13},
  year         = {2007},
}