Radiobiologic studies comparing Yttrium-90 irradiation and external beam irradiation in vitro

The purpose of this study was to compare the effectiveness of Yttrium-90 (Y-90) labeled antibody irradiation to 60Co external beam irradiation in vitro by colony formation assay. Two human colon carcinoma cell lines, LS174T, a high CEA producer, and WiDr, a low CEA producer, were exposed to specific activities of Y-90 labeled murine monoclonal anti-CEA antibody ranging from 2.5 to 30 microCi/ml for a fixed period of time. This resulted in calculated doses of 2.25 to 27 Gy and initial dose rates of 2.5 to 29 cGy/hr. Results were compared to similar doses of Y-90 labeled non-specific antibody, unlabeled specific and non-specific antibody, and 60Co external beam irradiation. External beam irradiation studies showed that WiDr, compared to LS174T, was more radioresistant with a larger shoulder to the survival curve, indicating a greater capacity for radiation-induced sublethal damage repair. WiDr was also more radioresistant to Y-90 antibody irradiation. When compared to external beam irradiation, Y-90 labeled antibody irradiation resulted in less cell killing by a factor of 2.4 for LS174T and 3.4 for WiDr. Unlabeled antibody had no significant effect on cell survival. Radiation-induced cell cycle delay experiments demonstrated that WiDr had less cell cycle delay (0.9 to 1.0 min/cGy) compared to LS174T (1.2 min/cGy) after single fraction external beam irradiation. Our results indicate that Y-90 low dose-rate irradiation is radiobiologically less effective in vitro than high dose-rate external beam irradiation by a factor of about 2.4 to 3.4. The results also suggest that the magnitude of this difference depends on the cell line's ability to repair sublethal radiation damage and the degree of cell cycle prolongation after irradiation.