COMPARISON OF I-131-LABELED AND Y-90 LABELED MONOCLONAL-ANTIBODY 17-1A FOR TREATMENT OF HUMAN COLON CANCER XENOGRAFTS

The choice of radionuclide remains an important question in clinical radioimmunotherapy. Therefore, a study was initiated, using an in vivo model system, to assess the relative merits of I-131- and Y-90-labeled 17-1A monoclonal antibody as therapeutic agents in the treatment of colon cancer. Iodine-131- and Y-90-labeled 17-1A were assessed in animal therapy trials using athymic nude mice bearing LS174T human colon cancer xenografts. Iodine-131-labeled 17-1A decreased tumor growth in a dose-dependent fashion without lethality. In contrast, the doses of Y-90-labeled 17-1A which were required to produce a significant increase in tumor doubling time also caused marked toxicity. Although similar tumor growth inhibition was produced by 250 muCi Y-90- and 150 muCi I-131-labeled 17-1A, Medical Internal Radiation Dose calculations based on biodistribution data estimated that the dose delivered by Y-90 was greater than that delivered by I-131. To investigate this discrepancy, 3-dimensional dose distributions within LS174T tumors were assessed using autoradiography and 3-dimensional calculational techniques. It was found that a greater fraction of the dose was deposited in the tumor after treatment with I-131- compared to Y-90-labeled 17-1A. When the Medical Internal Radiation Dose calculations were adjusted using the 3-dimensional dose distributions, 250 muCi of Y-90- and 150 muCi of I-131-labeled 17-1A were found to deliver similar tumor doses. These studies suggest that I-131-labeled 17-IA is superior to Y-90-labeled 17-1A, since I-131-labeled antibody produced less hematological and animal toxicity and was more effective at inhibiting LS174T tumor growth than Y-90-labeled antibody across the range of radionuclide doses tested. Furthermore, they suggest that it will be necessary to perform 3-dimensional dose calculations in addition to Medical Internal Radiation Dose calculations in order to interpret tumor dosimetry.