Interpreting the biological effects of protons as a function of physical quantity: linear energy transfer or microdosimetric lineal energy spectrum?

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Linear Energy Transfer* ; Protons* ; Relative Biological Effectiveness*; Humans ; Radiometry/methods ; Cell Line, Tumor ; Dose-Response Relationship, Radiation ; DNA Damage

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.
(© 2024. The Author(s).)

Sci Rep. 2020 Feb 21;10(1):3199. (PMID: 32081928)
Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):442-50. (PMID: 22099045)
Phys Med Biol. 2018 May 04;63(9):095011. (PMID: 29726401)
Int J Radiat Oncol Biol Phys. 2015 Nov 1;93(3):557-68. (PMID: 26460998)
Phys Med Biol. 2004 Jul 7;49(13):2811-25. (PMID: 15285249)
J ICRU. 2011 Dec;11(2):1-77. (PMID: 24174422)
Cancers (Basel). 2020 Dec 05;12(12):. (PMID: 33291477)
Radiat Res. 2012 Oct;178(4):341-56. (PMID: 22880622)
Int J Radiat Biol. 1996 Jun;69(6):739-55. (PMID: 8691026)
Sci Rep. 2015 May 18;5:9850. (PMID: 25984967)
Phys Med Biol. 2018 Dec 21;64(1):015008. (PMID: 30523805)
Precis Radiat Oncol. 2022 Jun;6(2):164-176. (PMID: 36160180)
Radiat Res. 2024 Feb 1;201(2):104-114. (PMID: 38178781)
Med Phys. 1998 Jul;25(7 Pt 1):1157-70. (PMID: 9682201)
Acta Oncol. 2013 Apr;52(3):580-8. (PMID: 22909391)
Radiat Res. 2022 Mar 1;197(3):218-232. (PMID: 34855935)
Med Phys. 2018 Nov;45(11):e925-e952. (PMID: 30421808)
Acta Oncol. 2017 Nov;56(11):1367-1373. (PMID: 28826292)
Phys Med Biol. 2022 Jun 10;67(12):. (PMID: 35545062)
Int J Radiat Oncol Biol Phys. 2010 Nov 15;78(4):1177-83. (PMID: 20732758)
Med Phys. 2019 Feb;46(2):1064-1074. (PMID: 30565705)
Radiat Prot Dosimetry. 2002;99(1-4):337-42. (PMID: 12194318)
Med Phys. 2019 Mar;46(3):e53-e78. (PMID: 30661238)
Phys Med Biol. 2014 Nov 21;59(22):R419-72. (PMID: 25361443)
J Thorac Oncol. 2014 Jul;9(7):965-973. (PMID: 24922006)
Radiat Res. 2008 Apr;169(4):447-59. (PMID: 18363426)
Radiat Environ Biophys. 2000 Sep;39(3):173-7. (PMID: 11095147)
Int J Part Ther. 2018 Summer;5(1):160-171. (PMID: 30338268)
Phys Med Biol. 2012 Mar 7;57(5):1159-72. (PMID: 22330133)
Int J Radiat Biol. 1998 Sep;74(3):397-403. (PMID: 9737542)
Br J Radiol. 2011 Dec;84 Spec No 1:S11-8. (PMID: 22374547)
Phys Med Biol. 2020 Feb 12;65(4):045005. (PMID: 31968318)
Int J Radiat Oncol Biol Phys. 2002 Jun 1;53(2):407-21. (PMID: 12023146)
Sci Rep. 2018 Oct 30;8(1):16063. (PMID: 30375461)
Phys Med Biol. 2015 Nov 7;60(21):8399-416. (PMID: 26459756)
Int J Radiat Oncol Biol Phys. 2011 Nov 15;81(4):1136-43. (PMID: 21075549)
Phys Med Biol. 2020 Dec 04;65(23):235010. (PMID: 33274727)
Radiat Res. 2013 Jan;179(1):21-8. (PMID: 23148508)
Int J Radiat Oncol Biol Phys. 2014 Sep 1;90(1):27-35. (PMID: 24986743)
Med Phys. 2015 Nov;42(11):6234-47. (PMID: 26520716)
Radiother Oncol. 2021 Aug;161:211-221. (PMID: 33894298)
Phys Med Biol. 2008 Jan 7;53(1):37-59. (PMID: 18182686)
Clin Oncol (R Coll Radiol). 2018 May;30(5):285-292. (PMID: 29454504)

Keywords: Linear energy transfer (LET); Lung cancer cells; Microdosimetric lineal energy spectrum; Proton biological effect

0 (Protons)

Date Created: 20241025 Date Completed: 20241025 Latest Revision: 20241028

20241028

PMC11502811

10.1038/s41598-024-73619-x

39448656