Improved tumor targeting and decreased normal tissue accumulation through extracorporeal affinity adsorption in a two-step pretargeting strategy.
OBJECTIVE
Evaluation of the possibilities of reducing the accumulation of radiolabeled streptavidin in radiosensitive organs by extracorporeal affinity adsorption (ECAT).


METHODS
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.
Mårtensson
Linda
L
Department of Oncology, University of Lund, Sweden. linda.martensson@med.lu.se
Nilsson
Rune
R
Ohlsson
Tomas
T
Sjögren
Hans-Olov
HO
Strand
Sven-Erik
SE
Tennvall
Jan
J
D000327:Adsorption; D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D005112:Extracorporeal Circulation; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000378:metabolism; D007205:Indium Radioisotopes / Q000493:pharmacokinetics*; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D008198:Lymph Nodes / Q000000981:diagnostic imaging / Q000378:metabolism; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D010179:Pancreas / Q000000981:diagnostic imaging / Q000378:metabolism; D011877:Radionuclide Imaging; D051381:Rats; D011914:Rats, Inbred BN; D019809:Streptavidin / Q000493:pharmacokinetics*; D014018:Tissue Distribution
C405616:DOTA-biotin; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D009942:Organometallic Compounds; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D001710:Biotin; D019809:Streptavidin