Abstract
BACKGROUND: Dose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy. Relatively few studies to date have investigated the dose rate effect in RNT. Therefore, the aim of this study was to benchmark (90)Y RNT (at different dose rates) against external beam radiotherapy (EBRT) in vitro and compare cell kill responses between the two irradiation processes. RESULTS: Three human colorectal carcinoma (CRC) cell lines (HT29, HCT116, SW48) were exposed to (90)Y doses in the ranges 1-10.4 and 6.2-62.3 Gy with initial dose rates of 0.013-0.13 Gy/hr (low dose rate, LDR) and 0.077-0.77 Gy/hr (high dose rate, HDR), respectively. Results were compared to a 6-MV photon beam doses in the range from 1-9 Gy with constant dose rate of 277 Gy/hr. The cell survival parameters from the linear quadratic (LQ) model were determined. Additionally, Monte Carlo simulations were performed to calculate the average dose, dose rate and the number of hits in the cell nucleus. For the HT29 cell line, which was the most radioresistant, the α/β ratio was found to be ≈ 31 for HDR-(90)Y and ≈ 3.5 for EBRT. LDR-(90)Y resulting in insignificant cell death compared to HDR-(90)Y and EBRT. Simulation results also showed for LDR-(90)Y, for doses ≲ 3 Gy, the average number of hits per cell nucleus is ≲ 2 indicating insufficiently delivered lethal dose. For (90)Y doses [Formula: see text] 3 Gy the number of hits per nucleus decreases rapidly and falls below ≈ 2 after ≈ 5 days of incubation time. Therefore, our results demonstrate that LDR-(90)Y is radiobiologically less effective than EBRT. However, HDR-(90)Y at ≈ 56 Gy was found to be radiobiologically as effective as acute ≈ 8 Gy EBRT. CONCLUSION: These results demonstrate that the efficacy of RNT is dependent on the initial dose rate at which radiation is delivered. Therefore, for a relatively long half-life radionuclide such as (90)Y, a higher initial activity is required to achieve an outcome as effective as EBRT.