Antibody localization to B-cell lymphoma xenografts in immunodeficient mice: importance of using residualizing radiolabels.
Antibody (Ab) localization to Raji B-cell lymphoma xenografts in severe combined immunodeficient (SCID) mice was investigated using three Abs: anti-CD20; anti-CD147; and anti-MHC class II. These antigens are all high-density cell surface antigens, and the Abs are all considered to be slowly internalized and catabolized, with catabolism primarily due to the basal turnover rate of cell surface constituents. Unexpectedly, specific Ab uptake was demonstrated only when residualizing labels were used. The residualizing labels tested were 111In-benzyl-diethylenetriaminepentaacetic acid and [125I]iodo-dilactitol-tyramine, whereas the nonresidualizing label was a conventional iodine label. In contrast, in vitro experiments demonstrated very slow catabolism of the same Abs. These data strongly suggest that Ab catabolism is much more rapid in vivo than in vitro and has a strong impact on Ab accumulation in the tumor. If autologous human tumors are similar to these xenografts, then there should be a large advantage in the use of residualizing radiolabels for radioimmunotherapy.
Michel
Rosana B
RB
Center for Molecular Medicine and Immunology, Belleville, New Jersey 07109, USA.
Ochakovskaya
Rita
R
Mattes
M Jules
MJ
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D005260:Female; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods*; D013997:Time Factors; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
D000906:Antibodies