Abstract
BackgroundDose 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 90Y RNT (at different dose rates) against external beam radiotherapy (EBRT) in vitro and compare cell kill responses between the two irradiation processes.ResultsThree human colorectal carcinoma (CRC) cell lines (HT29, HCT116, SW48) were exposed to 90Y 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–90Y and ≈ 3.5 for EBRT. LDR–90Y resulting in insignificant cell death compared to HDR–90Y and EBRT. Simulation results also showed for LDR–90Y, for doses ≲ 3 Gy, the average number of hits per cell nucleus is ≲ 2 indicating insufficiently delivered lethal dose. For 90Y doses gtrsim 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–90Y is radiobiologically less effective than EBRT. However, HDR–90Y at ≈ 56 Gy was found to be radiobiologically as effective as acute ≈ 8 Gy EBRT.ConclusionThese 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 90Y, a higher initial activity is required to achieve an outcome as effective as EBRT.
Highlights
Dose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy
We benchmarked the effectiveness of external beam radiotherapy (EBRT) to 90Y Radionuclide therapy (RNT) in vitro specific to CRC cell lines
For the HT29 cell line, we found α/β ≈ 31 for HDR–90Y compared to ≈ 3.5 for EBRT
Summary
Dose rate variation is a critical factor affecting radionuclide therapy (RNT) efficacy. Current clinical therapeutic radionuclides can be classified based on the nature of their radiation properties such as linear energy transfer (LET, which is defined as the energy deposition per unit length travelled); 50–230 keV/μm for alpha particle emitters, 0.2 keV/μm for beta emitters and 4–26 keV/μm for Auger electron emitters [7, 8]. Radionuclides such as 223Ra (α) ,177Lu (β) and 67Cu (β) which emit particles with a short range (relatively high LET) are used in Targeted RNT [3, 6]. Long-range radionuclide emitters can be labelled with nano- or micro-particles for SIRT [6]
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