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EJNMMI Phys. 2018 Sep 3;5(1):18. doi: 10.1186/s40658-018-0217-8.

Comparison of radiobiological parameters for 90Y radionuclide therapy (RNT) and external beam radiotherapy (EBRT) in vitro.

Author information

1
University of Sydney, School of Physics, Sydney, Australia.
2
University of Sydney, Discipline of Medical Radiation Science, Sydney, Australia.
3
Royal North Shore Hospital (RNSH), Department of Nuclear Medicine, Sydney, Australia.
4
Bill Walsh Translational Cancer Research Laboratory, The Kolling Institute, Northern Sydney Local Health District, Sydney, Australia.
5
Royal North Shore Hospital (RNSH), Department of Radiation Oncology, Sydney, Australia.
6
The University of Sydney Northern Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia.
7
University of Sydney, School of Physics, Sydney, Australia. dale.bailey@sydney.edu.au.
8
University of Sydney, Discipline of Medical Radiation Science, Sydney, Australia. dale.bailey@sydney.edu.au.
9
Royal North Shore Hospital (RNSH), Department of Nuclear Medicine, Sydney, Australia. dale.bailey@sydney.edu.au.

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 90Y 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 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 [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-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.

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 90Y, a higher initial activity is required to achieve an outcome as effective as EBRT.

KEYWORDS:

External beam radiotherapy (EBRT); Radionuclide therapy (RNT); Yttrium-90

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