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

Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5572s-5576s. doi: 10.1158/1078-0432.CCR-07-0891.

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 111In-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adsorption
  • Animals
  • Biotin / analogs & derivatives*
  • Biotin / metabolism
  • Biotin / pharmacokinetics
  • Colonic Neoplasms / diagnostic imaging*
  • Colonic Neoplasms / metabolism
  • Extracorporeal Circulation*
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Heterocyclic Compounds, 1-Ring / metabolism
  • Indium Radioisotopes / pharmacokinetics*
  • Liver / diagnostic imaging
  • Liver / metabolism
  • Lymph Nodes / diagnostic imaging
  • Lymph Nodes / metabolism
  • Organometallic Compounds / pharmacokinetics*
  • Pancreas / diagnostic imaging
  • Pancreas / metabolism
  • Radionuclide Imaging
  • Rats
  • Rats, Inbred BN
  • Streptavidin / pharmacokinetics*
  • Tissue Distribution

Substances

  • DOTA-biotin
  • Heterocyclic Compounds, 1-Ring
  • Indium Radioisotopes
  • Organometallic Compounds
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • Biotin
  • Streptavidin