Effect of pre-irradiation on radiopharmaceutical localization in human colon tumor xenografts using mono- and bispecific monoclonal antibodies.

In previous investigations we found that pre-irradiation of a tumor can significantly increase site-specific accumulation of radiolabeled monoclonal antibodies (MAb). The aims of the present study were to compare the effects of radiation on the localization of conventional MAb and a bifunctional delivery system and to evaluate a new time-dose schedule. T380 human colon tumors in athymic nude mice were irradiated (60Co, 10 Gy single dose) and the antibodies were injected 2 hours later. For mice given 111In-ZCE025, an anti-carcinoembryonic antigen (CEA) MAb, the biodistribution of activity was determined 7 days later. The animals receiving ECA001, a bispecific antibody binding to CEA and to a hapten on 111In-DBX, were injected with the radiolabeled hapten 5 days after cold annbody and sacrificed 2 days later. The mean percentage of injected dose (%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 for 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 of conventional MAb within solid tumors by over 200%. In addition, the efficacy of the approach can be enhanced by manipulation of the time-dose schedule. The results with the bispecific antibody system were unexpectedly confounded by significant differences in tumor growth rate after treatment a phenomenon not seen in the groups receiving the conventional MAb.