Development of a transmission alpha particle dosimetry technique using A549 cells and a Ra-223 source for targeted alpha therapy.
OBJECTIVE
In targeted radionuclide therapy, regional tumors are targeted with radionuclides delivering therapeutic radiation doses. Targeted alpha therapy (TAT) is of particular interest due to its ability to deliver alpha particles of high linear energy transfer within the confines of the tumor. However, there is a lack of data related to alpha particle distribution in TAT. These data are required to more accurately estimate the absorbed dose on a cellular level. As a result, there is a need for a dosimeter that can estimate, or better yet determine the absorbed dose deposited by alpha particles in cells. In this study, as an initial step, the authors present a transmission dosimetry design for alpha particles using A549 lung carcinoma cells, an external alpha particle emitting source (radium 223; Ra-223) and a Timepix pixelated semiconductor detector.


METHODS
The dose delivery to the A549 lung carcinoma cell line from a Ra-223 source, considered to be an attractive radionuclide for alpha therapy, was investigated in the current work. A549 cells were either unirradiated (control) or irradiated for 12, 1, 2, or 3 h with alpha particles emitted from a Ra-223 source positioned below a monolayer of A549 cells. The Timepix detector was used to determine the number of transmitted alpha particles passing through the A549 cells and DNA double strand breaks (DSBs) in the form of γ-H2AX foci were examined by fluorescence microscopy. The number of transmitted alpha particles was correlated with the observed DNA DSBs and the delivered radiation dose was estimated. Additionally, the dose deposited was calculated using Monte Carlo code SRIM.


RESULTS
Approximately 20% of alpha particles were transmitted and detected by Timepix. The frequency and number of γ-H2AX foci increased significantly following alpha particle irradiation as compared to unirradiated controls. The equivalent dose delivered to A549 cells was estimated to be approximately 0.66, 1.32, 2.53, and 3.96 Gy after 12, 1, 2, and 3 h irradiation, respectively, considering a relative biological effectiveness of alpha particles of 5.5.


CONCLUSIONS
The study confirmed that the Timepix detector can be used for transmission alpha particle dosimetry. If cross-calibrated using biological dosimetry, this method will give a good indication of the biological effects of alpha particles without the need for repeated biological dosimetry which is costly, time consuming, and not readily available.
Department of Medical Physics, Royal Adelaide Hospital, Adelaide 5000, Australia and School of Physical Sciences, University of Adelaide, Adelaide 5005, Australia.
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Al Darwish
Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide 5001, Australia and School of Medicine, University of Adelaide, Adelaide 5005, Australia.
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Staudacher
International Centre for Allied Health Evidence, Sansom Institute, University of South Australia, Adelaide 5001, Australia and Sansom Institute for Health Research, University of South Australia, Adelaide 5001, Australia.
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Y
Li
Translational Oncology Laboratory, Centre for Cancer Biology, SA Pathology and University of South Australia, Adelaide 5001, Australia; School of Medicine, University of Adelaide, Adelaide 5005, Australia; and Cancer Clinical Trials Unit, Royal Adelaide Hospital, Adelaide 5000, Australia.
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Brown
School of Physical Sciences, University of Adelaide, Adelaide 5005, Australia; International Centre for Allied Health Evidence, Sansom Institute, University of South Australia, Adelaide 5001, Australia; and Sansom Institute for Health Research, University of South Australia, Adelaide 5001, Australia.
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E
Bezak
D000072283:A549 Cells; D000512:Alpha Particles / Q000627:therapeutic use*; D002470:Cell Survival / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D011874:Radiometry / Q000295:instrumentation / Q000379:methods*
C468783:H2AX protein, human; D006657:Histones