Mouse-specific antibody responses to a monoclonal antibody during repeated immunoscintigraphy investigations: comparison of antibody titres and imaging studies in a rat model.

As a model for human mouse-specific antibody responses in patients undergoing immunoscintigraphy, we have investigated in rats the production of mouse-specific antibodies (MA) to the mouse monoclonal antibody 791T/36. At intervals of between 5 and 16 weeks the rats were given repeated cycles of intravenous (IV) injections of antibody with or without a simultaneous intradermal (ID) injection. The IV dose was 60 micrograms/kg, a dose similar to that used in many clinical immunoscintigraphy studies. The ID injection was 2 micrograms, which mimicks the skin test dose often given in clinical imaging protocols. The study was carried out with both 131I-labelled antibody and with antibody labelled with 111In by diethylenetriamine-penta-acetic acid (DTPA) chelation. MA was measured with a passive haemagglutination assay using sheep red blood cells coated with the monoclonal antibody. Of rats given ID injections of unlabelled antibody at the same time as the IV imaging doses, 9/20 produced MA during 4 cycles of injections. In contrast, only 2/16 rats given only the IV dose produced MA. Both 131I- and 111In-labelled antibody appeared equally immunogenic with 5/18 and 6/18 overall responders, respectively. The production of MA was associated with a significant perturbation in the biodistribution of the IV dose of labelled antibody as seen by gamma-camera imaging of the rats given 111In-labelled antibody. There was clearance of immune complexes to the liver, this organ accumulating up to 90% of the whole body count rate of radiolabel. MA titres of between 1/100 and 1/78,000 caused equal perturbation of biodistribution, although below 1/100 the effect was more variable.