The impact of cell proliferation and radionuclide uptake rate in radio-immunotherapy

Abstract

Purpose The instantaneous-uptake model of O’Donoghue [”The impact of tumor cell proliferation in radio-immunotherapy”, Cancer 73, 974–980 (1994)] for a proliferating cell population irradiated by an exponentially decreasing dose-rate is being extended to arbitrary uptake rates of the radiopharmaceutical in tumor cells. Methods The time derivative of the survival curve is examined and an expression for the minimum of the surviving fraction is deduced along with a new expression for the biological effective dose (BED). Surviving fractions are calculated over a clinically relevant parameter range to establish general trends. Results Results are presented for the therapy radionuclides Y-90, I-131, and P-32, assuming uptake half-times 1–24 h, extrapolated initial dose-rates 0.5–1 Gy h-1 and a biological clearance half-life of 7 days. Cell doubling time equals 2 days. The exponential-uptake rate of the radiopharmaceutical by the targeted cells appears to have a considerable effect on the survival of a proliferating cell population (even for uptake half-times of only a few hours) and thence might need to be considered in the radiobiological models of tumor cell-kill in radio-immunotherapy. The differences between the exponential-uptake model and the instantaneous-uptake model become larger for high peak dose-rates, slow uptakes, and (slightly) for radionuclides with higher half-life. Moreover, the sensitivity of the cell survival on the uptake was found to be higher for the tumor cells with higher radio-sensitivity. Conclusion Neglecting an uptake phase may result in a considerable overestimation of cell kill.