THE ADVANTAGE OF RESIDUALIZING RADIOLABELS FOR TARGETING B-CELL LYMPHOMAS WITH A RADIOLABELED ANTI-CD22 MONOCLONAL-ANTIBODY

CD22 antibodies (Abs) bound to B-cell lymphomas are known to be intern alized and catabolized vapidly. Therefore, it would be expected that u se of CD22 as a target for radioimmunotherapy should be enhanced by th e use of ''residualizing'' radiolabels, which are trapped within the c ell after catabolism of the Ab to which they had been conjugated. Our study was intended to evaluate this hypothesis using Ab LL2. In initia l experiments, we found that LL2 binding was strongly temperature depe ndent, with approximately 15-fold greater binding at 37 degrees C than at 0 degrees C. A series of experiments suggested that this differenc e is due to a conformational change in the antigen at low temperature, so that the LL2 epitope is partially blocked. In vitro, residualizing labels-including I-125-dilactitol tyramine and In-111-DTPA-were retai ned by cells much longer than a conventional iodine label. In vivo, re sidualizing labels also showed a marked advantage in terms of uptake b y Ramos B-cell lymphoma xenografts in nude mice. However, the absolute Ab uptake by xenografts was quite low, in comparison with results obt ained with many carcinoma xenografts, which appears to be due in part to vascular properties of the B-cell lymphoma xenografts. (C) 1997 Wil ey-Liss, Inc.