Modulation of antibody kinetics by the cell membrane active agent tween 80 in vivo.
The modulation of antibody uptake by the tumour has been crucial in many radioantibody applications for delivering optimal dose for therapy. Our approach was to modulate the monoclonal antibody (MAb) uptake by using a surface detergent (Tween 80). Our Mab was raised against the tyrosine kinase receptor recombinant protein tie. Mice bearing Lewis lung carcinoma xenografts were studied after injecting I-125 labeled IgG1 subclass monoclonal antibody 3c4c7g6 tie protein. The biodistribution was studied at 4, 24, 48, 72, 96 and 120 hours after intravenous injection. Tween 80 was administered intratumourally, 0.04% of tumour volume. Without Tween 80 the antibody half-lives in tumour were 90 hours, in blood 39 hours, in liver 22 hours, and in kidney 52 hours, whereas using intratumoural Tween 80 half-lives were in tumour 66 hours, in blood 26 hours, in liver 27.5 hours and in kidney 27.5 hours. Although the Tween manipulation did not increase uptakes by organs, it did enhance clearance rate from the blood. This data indicates that antibody dose can be optimized by surface detergent, enhancing clearance without any burden to critical organs. This might be crucial in adjusting delivered radioimmunotherapy dose by changing the mean residence time of an antibody.
Kairemo
K A
KA
Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
Karnani
P
P
Jekunen
A P
AP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000378:metabolism*; D018827:Carcinoma, Lewis Lung / Q000097:blood / Q000378:metabolism; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011136:Polysorbates / Q000494:pharmacology*; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011136:Polysorbates; D013501:Surface-Active Agents