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

Author:
  • Linda Mårtensson
  • Rune Nilsson
  • Tomas G Ohlsson
  • Hans Olof Sjögren
  • Sven-Erik Strand
  • Jan Tennvall
Publishing year: 2007
Language: English
Pages: 5572-5576
Publication/Series: Clinical Cancer Research
Volume: 13
Issue: 18
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1078-0432
Sven-Erik Strand
E-mail: sven-erik.strand [at] med.lu.se

Project manager

Systemic Radiation Therapy Group

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Professor emeritus

Medical Radiation Physics, Lund

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