EFFECT OF PREIRRADATION ON RADIOPHARMACEUTICAL LOCALIZATION IN HUMAN COLON-TUMOR XENOGRAFTS USING MONOSPECIFIC AND BISPECIFIC MONOCLONAL-ANTIBODIES

In previous investigations we found that pre-irradiation of a tumor ca n significantly increase site-specific accumulation of radiolabeled mo noclonal antibodies (MAb). The aims of the present study were to compa re the effects of radiation on the localization of conventional MAb an d a bifunctional delivery system and to evaluate a new time-dose sched ule. T380 human colon tumors in athymic nude mice were ii-radiated (Co -60, 10 Gy single dose) and the antibodies were injected 2 hours later : For mice given (111)ln-ZCE025, an anti-carcinoembryonic antigen (CEA ) MAb, the biodistribution of activity was determined 7 days later. Th e animals receiving ECA001, a bispecific antibody binding to CEA and t o a hapten on (111)ln-DBX were injected with the radiolabeled hapten 5 days after cold annbody and sacrificed 2 days later. The mean percent age of injected nose (%ID/g) within tumors was significantly increased (p<0.05) for both anti-CEA antibodies after pre-irradiation compared to their respective nonirradiated controls (%ID/g = 22.8 versus 47.8 f or conventional MAb; %ID/g = 12.5 versus 25.9 for bifunctional system) . Tumor-to-normal tissue ranos were also higher in the pre-irradiated groups. The data show that pre-irradiation can increase the delivery o f conventional MAb within solid tumors by over 200%. In addition, the efficacy of the approach can be enhanced by manipulation of the time-c lose schedule. The results with the bispecific antibody system were un expectedly confounded by significant differences in tumor growth rate after treatment, a phenomenon not seen in the groups receiving the con ventional MAb.