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

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@article{2d7c266685e34c20865bff19585fdb2a,
title = "Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy",
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 = "Linda M{\aa}rtensson and Rune Nilsson and Ohlsson, {Tomas G} and Sj{\"o}gren, {Hans Olof} and Sven-Erik Strand and Jan Tennvall",
year = "2007",
doi = "10.1158/1078-0432.CCR-07-0891",
language = "English",
volume = "13",
pages = "5572S--5576S",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research",
number = "18",

}