Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum?
Abstract The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all th...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-10-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-73619-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850204275946291200 |
|---|---|
| author | Fada Guan Lawrence Bronk Matthew Kerr Yuting Li Leslie A. Braby Mary Sobieski Xiaochun Wang Xiaodong Zhang Clifford Stephan David R. Grosshans Radhe Mohan |
| author_facet | Fada Guan Lawrence Bronk Matthew Kerr Yuting Li Leslie A. Braby Mary Sobieski Xiaochun Wang Xiaodong Zhang Clifford Stephan David R. Grosshans Radhe Mohan |
| author_sort | Fada Guan |
| collection | DOAJ |
| description | Abstract The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The primary advantage of using the “dose and LET” physical system is its relative simplicity, especially for presenting and recording results. Inclusion of additional information such as the energy spectrum of charged particles renders this approach adequate to describe the biological effects of large dose levels from homogeneous sources. The primary disadvantage of this system is that it does not provide a unique description of the stochastic nature of radiation interactions. We and others have used dose-averaged LET (LET d ) as a correlative physical quantity to the relative biological effectiveness (RBE) of proton beams. This approach is based on established experimental findings that proton RBE increases with LET d . However, this approach might not be applicable to intensity-modulated proton therapy or other applications in which the proton energy spectrum is highly heterogeneous. In the current study, we irradiated cancer cells with scanning proton beams with identical LET d (3.4 keV/µm) but arising from two different proton energy/LET spectra (a narrow spectrum in group 1 and a widespread heterogeneous spectrum in group 2). Clonogenic survival after irradiation revealed significant differences in RBE at any cell surviving fraction: e.g., at a surviving fraction of 0.1, the RBE was 0.97 ± 0.03 in group 1 and 1.16 ± 0.04 in group 2 (p≤0.01), validating our hypothesis that LET d alone may not adequately indicate proton RBE. Further analysis showed that microdosimetric spectrum (the probability density function of the stochastic physical quantity lineal energy y) was helpful for interpreting observed differences in biological effects. However, more accurate use of microdosimetric spectrum to quantify RBE requires a cell line–specific mechanistic model. |
| format | Article |
| id | doaj-art-d86dbeec3d114ee9ab2a00ecde7d8cc1 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-d86dbeec3d114ee9ab2a00ecde7d8cc12025-08-20T02:11:18ZengNature PortfolioScientific Reports2045-23222024-10-0114111110.1038/s41598-024-73619-xInterpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum?Fada Guan0Lawrence Bronk1Matthew Kerr2Yuting Li3Leslie A. Braby4Mary Sobieski5Xiaochun Wang6Xiaodong Zhang7Clifford Stephan8David R. Grosshans9Radhe Mohan10Department of Therapeutic Radiology, Yale University School of MedicineDepartment of Radiation Physics, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Physics, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Physics, The University of Texas MD Anderson Cancer CenterDepartment of Nuclear Engineering, Texas A&M UniversityCenter for Translational Cancer Research, Texas A&M Health Science Center, Institute of Biosciences and TechnologyDepartment of Radiation Physics, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Physics, The University of Texas MD Anderson Cancer CenterCenter for Translational Cancer Research, Texas A&M Health Science Center, Institute of Biosciences and TechnologyDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer CenterDepartment of Radiation Physics, The University of Texas MD Anderson Cancer CenterAbstract The choice of appropriate physical quantities to characterize the biological effects of ionizing radiation has evolved over time coupled with advances in scientific understanding. The basic hypothesis in radiation dosimetry is that the energy deposited by ionizing radiation initiates all the consequences of exposure in a biological sample (e.g., DNA damage, reproductive cell death). Physical quantities defined to characterize energy deposition have included dose, a measure of the mean energy imparted per unit mass of the target, and linear energy transfer (LET), a measure of the mean energy deposition per unit distance that charged particles traverse in a medium. The primary advantage of using the “dose and LET” physical system is its relative simplicity, especially for presenting and recording results. Inclusion of additional information such as the energy spectrum of charged particles renders this approach adequate to describe the biological effects of large dose levels from homogeneous sources. The primary disadvantage of this system is that it does not provide a unique description of the stochastic nature of radiation interactions. We and others have used dose-averaged LET (LET d ) as a correlative physical quantity to the relative biological effectiveness (RBE) of proton beams. This approach is based on established experimental findings that proton RBE increases with LET d . However, this approach might not be applicable to intensity-modulated proton therapy or other applications in which the proton energy spectrum is highly heterogeneous. In the current study, we irradiated cancer cells with scanning proton beams with identical LET d (3.4 keV/µm) but arising from two different proton energy/LET spectra (a narrow spectrum in group 1 and a widespread heterogeneous spectrum in group 2). Clonogenic survival after irradiation revealed significant differences in RBE at any cell surviving fraction: e.g., at a surviving fraction of 0.1, the RBE was 0.97 ± 0.03 in group 1 and 1.16 ± 0.04 in group 2 (p≤0.01), validating our hypothesis that LET d alone may not adequately indicate proton RBE. Further analysis showed that microdosimetric spectrum (the probability density function of the stochastic physical quantity lineal energy y) was helpful for interpreting observed differences in biological effects. However, more accurate use of microdosimetric spectrum to quantify RBE requires a cell line–specific mechanistic model.https://doi.org/10.1038/s41598-024-73619-xProton biological effectLinear energy transfer (LET)Microdosimetric lineal energy spectrumLung cancer cells |
| spellingShingle | Fada Guan Lawrence Bronk Matthew Kerr Yuting Li Leslie A. Braby Mary Sobieski Xiaochun Wang Xiaodong Zhang Clifford Stephan David R. Grosshans Radhe Mohan Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum? Scientific Reports Proton biological effect Linear energy transfer (LET) Microdosimetric lineal energy spectrum Lung cancer cells |
| title | Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum? |
| title_full | Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum? |
| title_fullStr | Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum? |
| title_full_unstemmed | Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum? |
| title_short | Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum? |
| title_sort | interpreting the biological effects of protons as a function of physical quantity linear energy transfer or microdosimetric lineal energy spectrum |
| topic | Proton biological effect Linear energy transfer (LET) Microdosimetric lineal energy spectrum Lung cancer cells |
| url | https://doi.org/10.1038/s41598-024-73619-x |
| work_keys_str_mv | AT fadaguan interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT lawrencebronk interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT matthewkerr interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT yutingli interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT leslieabraby interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT marysobieski interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT xiaochunwang interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT xiaodongzhang interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT cliffordstephan interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT davidrgrosshans interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum AT radhemohan interpretingthebiologicaleffectsofprotonsasafunctionofphysicalquantitylinearenergytransferormicrodosimetriclinealenergyspectrum |