TY - JOUR
T1 - Mapping the relative biological effectiveness of proton, helium and carbon ions with high-throughput techniques
AU - Bronk, Lawrence
AU - Guan, Fada
AU - Patel, Darshana
AU - Ma, Duo
AU - Kroger, Benjamin
AU - Wang, Xiaochun
AU - Tran, Kevin
AU - Yiu, Joycelyn
AU - Stephan, Clifford
AU - Debus, Jürgen
AU - Abdollahi, Amir
AU - Jäkel, Oliver
AU - Mohan, Radhe
AU - Titt, Uwe
AU - Grosshans, David R.
N1 - Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.
AB - Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.
KW - Charged particle therapy
KW - High-throughput techniques
KW - Lung cancer cells
KW - Relative biological effectiveness
UR - http://www.scopus.com/inward/record.url?scp=85097313658&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85097313658&partnerID=8YFLogxK
U2 - 10.3390/cancers12123658
DO - 10.3390/cancers12123658
M3 - Article
C2 - 33291477
AN - SCOPUS:85097313658
SN - 2072-6694
VL - 12
SP - 1
EP - 15
JO - Cancers
JF - Cancers
IS - 12
M1 - 3658
ER -