Background: The purpose of this investigation was to compare the therapeutic effectiveness of yttrium-90 (90Y)-labeled monoclonal antibodies (MoAbs) with iodine-131 (131I)-labeled MoAbs delivered to human tumor xenografts at their maximum tolerated doses (MTD).
Methods: Nude mice bearing size-matched human lung adenocarcinoma xenografts (Calu-3) with mean tumor dimensions of approximately 0.8 cm received intravenous injections of the MTD of either 90Y- or 131I-labeled MoAbs. The mice received 125 microCi of 90Y-RS11 or 90Y-RS7, or 300 microCi of 131I-RS11 or 131I-RS7. Tumor size was measured weekly. Body weight and blood counts were monitored to measure toxicity.
Results: The calculated average radiation doses delivered to tumors in mice treated with 90Y-RS11 and 90Y-RS7 were 3578 and 3787 centigray (cGy), respectively, versus 1264 and 1368 cGy for 131I-RS11 and 131I-RS7, respectively. These values were calculated taking into consideration the tumor size-dependent absorbed fractions for the beta particles of both radioisotopes. The calculated radiation doses absorbed in the tumor correlated with the tumor responses observed. Mean tumor volume decreases at nadir were 66% and 87% after 90Y-RS11 and 90Y-RS7 therapy, respectively, with 15 of 30 mice treated with either MoAb having complete regression of their tumors. In contrast, only mean stable disease was observed with the 131I MoAb treatments.
Conclusions: The results demonstrate the superiority of 90Y-labeled MoAbs over conventionally labeled 131I-labeled MoAbs for therapy in this model. The fact that a substantial percentage of complete remissions was achieved with 90Y-labeled MoAbs suggests a considerable radiosensitivity of the tumor studied, and supports the suitability of choosing this tumor type as an attractive target for future clinical radioimmunotherapy.