A theoretical radiobiological assessment of the influence of radionuclide half-life on tumor response in targeted radiotherapy when a constant kidney toxicity is maintained

The potential of targeted radionuclide therapy may he limited if the antibody affinity to the tumor is relatively low and if significant normal tissue damage occurs while the tumor is sterilized. One way to increase the efficiency of the antibody-radionuclide complex might be to use knowledge of the radiobiological processes to select a near-optimal radionuclide half-life. In this paper, the role of physical half-life in targeted radiotherapy optimization is investigated using the linear quadratic (LQ) radiobiological model in conjunction with a range of radiobiological parameters relevant to the tumor. Five radionuclides (At-211, Y-90, I-131, Rb-86, and In-114) were selected, providing a half-life range from 0.3-49.5 days. The dose-limiting organ was assumed to be the kidney, with a simple fractional link between the initial (extrapolated) dose-rate to the tumor and the initial dose-rate to the kidney. The results suggest that short-lived radionuclides (half-life in the range of 1-10 days) have an advantage over medium- and long-lived radionuclides. Furthermore, for very rapid tumor uptake (uptake half-time of a few hours), very short-lived radionuclides (half-life of less than 1 day) could be efficiently employed. Ultimately, however, treatment outcome (in terms of tumor cell kill) is limited by the antibody affinity to the tumor.