A rat model for imaging the effect of anti mouse antibody responses on the biodistribution of radiolabelled mouse monoclonal antibodies

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Abstract
Rats were injected both intradermally and intravenously with an IgG2b mouse monoclonal antibody (791T/36) and subsequently the biodistribution of intravenously injected 111In labelled antibody was examined by gamma camera imaging in these and control rats. The majority of pretreated rats showed a marked perturbation of the biodistribution of the radiolabelled antibody with a marked increase of tracer in the liver. There was similar perturbation of the biodistribution of subsequently administered 111In labelled Fab fragment of the 791T/36 antibody and of another IgG2b monoclonal antibody. In contrast, there was little influence on the biodistribution of IgG2a or IgG1 monoclonal antibodies, indicating that the response in the rats was predominantly against the IgG2b isotype. This rat model system is amenable to examination of a number of aspects of the biological consequences of immune responses to foreign immunoglobulins relevant to their use for clinical imaging.