Skip to main content
Top
Published in: EJNMMI Research 1/2020

Open Access 01-12-2020 | Original research

Double-strand breaks in lymphocyte DNA of humans exposed to [18F]fluorodeoxyglucose and the static magnetic field in PET/MRI

Authors: Gunnar Brix, Elisabeth Günther, Ute Rössler, David Endesfelder, Alexandra Kamp, Ambros Beer, Matthias Eiber

Published in: EJNMMI Research | Issue 1/2020

Login to get access

Abstract

Background

Given the increasing clinical use of PET/MRI, potential risks to patients from simultaneous exposure to ionising radiation and (electro)magnetic fields should be thoroughly investigated as a precaution. With this aim, the genotoxic potential of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and a strong static magnetic field (SMF) were evaluated both in isolation and in combination using the γH2AX assay detecting double-strand breaks in lymphocyte DNA.

Methods

Thirty-two healthy young volunteers allocated to three study arms were exposed to [18F]FDG alone, to a 3-T SMF alone or to both combined over 60 min at a PET/CT or a PET/MRI system. Blood samples taken after in vivo exposure were incubated up to 60 min to extend the irradiation of blood by residual [18F]FDG within the samples and the time to monitor the γH2AX response. Absorbed doses to lymphocytes delivered in vivo and in vitro were estimated individually for each volunteer exposed to [18F]FDG. γH2AX foci were scored automatically by immunofluorescence microscopy.

Results

Absorbed doses to lymphocytes exposed over 60 to 120 min to [18F]FDG varied between 1.5 and 3.3 mGy. In this time interval, the radiotracer caused a significant median relative increase of 28% in the rate of lymphocytes with at least one γH2AX focus relative to the background rate (p = 0.01), but not the SMF alone (p = 0.47). Simultaneous application of both agents did not result in a significant synergistic or antagonistic outcome (p = 0.91).

Conclusion

There is no evidence of a synergism between [18F]FDG and the SMF that may be of relevance for risk assessment of PET/MRI.
Literature
1.
go back to reference C. Catana C. Principles of simultaneous PET/MR Imaging. Magn Reson Imaging Clin N Am. 2017;25(2):231-243. C. Catana C. Principles of simultaneous PET/MR Imaging. Magn Reson Imaging Clin N Am. 2017;25(2):231-243.
2.
go back to reference Aiello M, Cavaliere C, Marchitelli R, d'Albore A, De Vita E, Salvatore M. Hybrid PET/MRI methodology. Int Rev Neurobiol. 2018;141:97–128.CrossRef Aiello M, Cavaliere C, Marchitelli R, d'Albore A, De Vita E, Salvatore M. Hybrid PET/MRI methodology. Int Rev Neurobiol. 2018;141:97–128.CrossRef
3.
go back to reference Mannheim JG, Schmid AM, Schwenck J, et al. PET/MRI hybrid systems. Semin Nucl Med. 2018;48(4):332–47.CrossRef Mannheim JG, Schmid AM, Schwenck J, et al. PET/MRI hybrid systems. Semin Nucl Med. 2018;48(4):332–47.CrossRef
4.
go back to reference Ehman EC, Johnson GB, Villanueva-Meyer JE, et al. PET/MRI: Where might it replace PET/CT? J Magn Resonance Imaging. 2017;46(5):1247–62.CrossRef Ehman EC, Johnson GB, Villanueva-Meyer JE, et al. PET/MRI: Where might it replace PET/CT? J Magn Resonance Imaging. 2017;46(5):1247–62.CrossRef
5.
go back to reference Beyer T, Hacker M, Goh V. PET/MRI-knocking on the doors of the rich and famous. Br J Radiol. 2017;90(1077):20170347.CrossRef Beyer T, Hacker M, Goh V. PET/MRI-knocking on the doors of the rich and famous. Br J Radiol. 2017;90(1077):20170347.CrossRef
6.
go back to reference Broski SM, Goenka AH, Kemp BJ, Johnson GB. Clinical PET/MRI: 2018 update. AJR Am J Roentgenol. 2018;211(2):295–313.CrossRef Broski SM, Goenka AH, Kemp BJ, Johnson GB. Clinical PET/MRI: 2018 update. AJR Am J Roentgenol. 2018;211(2):295–313.CrossRef
7.
go back to reference Miles KA, Voo SA, Groves AM. Additional clinical value for PET/MRI in oncology: Moving beyond simple diagnosis. J Nucl Med. 2018;59(7):1028–32.CrossRef Miles KA, Voo SA, Groves AM. Additional clinical value for PET/MRI in oncology: Moving beyond simple diagnosis. J Nucl Med. 2018;59(7):1028–32.CrossRef
8.
go back to reference Brix G, Lechel U, Glatting G, et al. Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations. J Nucl Med. 2005;46:608–13.PubMed Brix G, Lechel U, Glatting G, et al. Radiation exposure of patients undergoing whole-body dual-modality 18F-FDG PET/CT examinations. J Nucl Med. 2005;46:608–13.PubMed
9.
go back to reference Brix G, Nekolla EA, Borowski M, Noßke D. Radiation risk and protection of patients in clinical SPECT/CT. Eur J Nucl Med Mol Imaging. 2014;41(Suppl 1):S125–36.CrossRef Brix G, Nekolla EA, Borowski M, Noßke D. Radiation risk and protection of patients in clinical SPECT/CT. Eur J Nucl Med Mol Imaging. 2014;41(Suppl 1):S125–36.CrossRef
10.
go back to reference Brix G. Risks and safety issues related to MR examinations. In: Reiser M, Semmler W, Hricak H, editors. Magnetic resonance tomography. Berlin, Heidelberg, New York: Springer; 2007. p. 153–67. Brix G. Risks and safety issues related to MR examinations. In: Reiser M, Semmler W, Hricak H, editors. Magnetic resonance tomography. Berlin, Heidelberg, New York: Springer; 2007. p. 153–67.
11.
go back to reference International Electrotechnical Commission. IEC 60601-2-33 (3.2 edition). Particular requirements for the safety of magnetic resonance equipment for medical diagnosis. 2015. International Electrotechnical Commission. IEC 60601-2-33 (3.2 edition). Particular requirements for the safety of magnetic resonance equipment for medical diagnosis. 2015.
12.
go back to reference Brix G, Nekolla EA, Nosske D, Griebel J. Risks and safety aspects related to PET/MR examinations. Eur J Nucl Med Mol Imaging. 2009;36(Suppl 1):S131–8.CrossRef Brix G, Nekolla EA, Nosske D, Griebel J. Risks and safety aspects related to PET/MR examinations. Eur J Nucl Med Mol Imaging. 2009;36(Suppl 1):S131–8.CrossRef
13.
go back to reference Mohajer JK, Nisbet A, Velliou E, Ajaz M, Schettino G. Biological effects of static magnetic field exposure in the context of MR-guided radiotherapy. Br J Radiol. 2019;92(1094):20180484.CrossRef Mohajer JK, Nisbet A, Velliou E, Ajaz M, Schettino G. Biological effects of static magnetic field exposure in the context of MR-guided radiotherapy. Br J Radiol. 2019;92(1094):20180484.CrossRef
14.
go back to reference Bug MU, Gargioni E, Guatelli S, et al. Effect of a magnetic field on the track structure of low-energy electrons: a Monte Carlo study. Eur Phys J D. 2010;60:85–92.CrossRef Bug MU, Gargioni E, Guatelli S, et al. Effect of a magnetic field on the track structure of low-energy electrons: a Monte Carlo study. Eur Phys J D. 2010;60:85–92.CrossRef
15.
go back to reference Lazarakis P, Bug MU, Gargioni E, et al. Effect of a static magnetic field on nanodosimetric quantities in a DNA volume. Int J Radiat Biol. 2012;88(1-2):183–8.CrossRef Lazarakis P, Bug MU, Gargioni E, et al. Effect of a static magnetic field on nanodosimetric quantities in a DNA volume. Int J Radiat Biol. 2012;88(1-2):183–8.CrossRef
16.
go back to reference Löbrich M, Rief N, Kuhne M, et al. In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc Natl Acad Sci USA. 2005;102:8984–9.CrossRef Löbrich M, Rief N, Kuhne M, et al. In vivo formation and repair of DNA double-strand breaks after computed tomography examinations. Proc Natl Acad Sci USA. 2005;102:8984–9.CrossRef
17.
go back to reference Shi L, Tashiro S. Estimation of the effects of medical diagnostic radiation exposure based on DNA damage. J Radiat Res. 2018;59(suppl_2):ii121–9.CrossRef Shi L, Tashiro S. Estimation of the effects of medical diagnostic radiation exposure based on DNA damage. J Radiat Res. 2018;59(suppl_2):ii121–9.CrossRef
18.
go back to reference May MS, Brand M, Wuest W, et al. Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing 18F-FDG PET/CT examinations. Eur J Nucl Med Mol Imaging. 2012;39(11):1712–9.CrossRef May MS, Brand M, Wuest W, et al. Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing 18F-FDG PET/CT examinations. Eur J Nucl Med Mol Imaging. 2012;39(11):1712–9.CrossRef
19.
go back to reference Schnarr K, Carter TF, Gillis D, et al. Biological response of positron emission tomography scan exposure and adaptive response in humans. Dose Response. 2015;13(4):1559325815611904.CrossRef Schnarr K, Carter TF, Gillis D, et al. Biological response of positron emission tomography scan exposure and adaptive response in humans. Dose Response. 2015;13(4):1559325815611904.CrossRef
20.
go back to reference Lancellotti P, Nchimi A, Delierneux C, et al. Biological effects of cardiac magnetic resonance on human blood cells. Circ Cardiovasc Imaging. 2015;8(9):e003697.CrossRef Lancellotti P, Nchimi A, Delierneux C, et al. Biological effects of cardiac magnetic resonance on human blood cells. Circ Cardiovasc Imaging. 2015;8(9):e003697.CrossRef
21.
go back to reference Reddig A, Fatahi M, Friebe B, et al. Analysis of DNA double-strand breaks and cytotoxicity after 7 Tesla magnetic resonance imaging of isolated human lymphocytes. PLoS One. 2015;10(7):e0132702.CrossRef Reddig A, Fatahi M, Friebe B, et al. Analysis of DNA double-strand breaks and cytotoxicity after 7 Tesla magnetic resonance imaging of isolated human lymphocytes. PLoS One. 2015;10(7):e0132702.CrossRef
22.
go back to reference Critchley WR, Reid A, Morris J, et al. The effect of 1.5 T cardiac magnetic resonance on human circulating leucocytes. Eur Heart J. 2018;39(4):305–12.CrossRef Critchley WR, Reid A, Morris J, et al. The effect of 1.5 T cardiac magnetic resonance on human circulating leucocytes. Eur Heart J. 2018;39(4):305–12.CrossRef
23.
go back to reference Fasshauer M, Krüwel T, Zapf A, et al. Absence of DNA double-strand breaks in human peripheral blood mononuclear cells after 3 Tesla magnetic resonance imaging assessed by γH2AX flow cytometry. Eur Radiol. 2018;28(3):1149–56.CrossRef Fasshauer M, Krüwel T, Zapf A, et al. Absence of DNA double-strand breaks in human peripheral blood mononuclear cells after 3 Tesla magnetic resonance imaging assessed by γH2AX flow cytometry. Eur Radiol. 2018;28(3):1149–56.CrossRef
24.
go back to reference Suntharalingam S, Mladenov E, Sarabhai T, et al. Abdominopelvic 1.5-T and 3.0-T MR imaging in healthy volunteers: Relationship to formation of DNA double-strand breaks. Radiology. 2018:529–35. Suntharalingam S, Mladenov E, Sarabhai T, et al. Abdominopelvic 1.5-T and 3.0-T MR imaging in healthy volunteers: Relationship to formation of DNA double-strand breaks. Radiology. 2018:529–35.
25.
go back to reference Kuo LJ, Yang LX. Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo. 2008;22(3):305–9.PubMed Kuo LJ, Yang LX. Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo. 2008;22(3):305–9.PubMed
26.
go back to reference Ivashkevich A, Redon CE, Nakamura AJ, Martin RF, Martin OA. Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research. Cancer Lett. 2012;327(1-2):123–33.CrossRef Ivashkevich A, Redon CE, Nakamura AJ, Martin RF, Martin OA. Use of the γ-H2AX assay to monitor DNA damage and repair in translational cancer research. Cancer Lett. 2012;327(1-2):123–33.CrossRef
27.
go back to reference Salimi M, Mozdarani H. γ-H2AX as a protein biomarker for radiation exposure response in ductal carcinoma breast tumors: Experimental evidence and literature review. Int J Radiat Res. 2014;12(1):1–11. Salimi M, Mozdarani H. γ-H2AX as a protein biomarker for radiation exposure response in ductal carcinoma breast tumors: Experimental evidence and literature review. Int J Radiat Res. 2014;12(1):1–11.
28.
go back to reference Ji J, Zhang Y, Redon CE, Reinhold WC, et al. Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay. PLoS One. 2017;12(2):e0171582.CrossRef Ji J, Zhang Y, Redon CE, Reinhold WC, et al. Phosphorylated fraction of H2AX as a measurement for DNA damage in cancer cells and potential applications of a novel assay. PLoS One. 2017;12(2):e0171582.CrossRef
29.
go back to reference Pasqualetti G, Gori G, Blandizzi C, Tacca M. Healthy volunteers and early phases of clinical experimentation. Eur J Clin Pharmacol. 2010;66(7):647–53.CrossRef Pasqualetti G, Gori G, Blandizzi C, Tacca M. Healthy volunteers and early phases of clinical experimentation. Eur J Clin Pharmacol. 2010;66(7):647–53.CrossRef
30.
go back to reference Karlberg AM, Sæther O, Eikenes L, Goa PA. Quantitative comparison of PET performance - Siemens Biograph mCT and mMR. EJNMMI Phys. 2016;3(1):5.CrossRef Karlberg AM, Sæther O, Eikenes L, Goa PA. Quantitative comparison of PET performance - Siemens Biograph mCT and mMR. EJNMMI Phys. 2016;3(1):5.CrossRef
31.
go back to reference Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 1962;51(2):224–32.PubMed Nadler SB, Hidalgo JH, Bloch T. Prediction of blood volume in normal human adults. Surgery. 1962;51(2):224–32.PubMed
32.
go back to reference Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry--standardization of nomenclature. J Nucl Med. 2009;50(3):477–84.CrossRef Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry--standardization of nomenclature. J Nucl Med. 2009;50(3):477–84.CrossRef
33.
go back to reference Hays MT, Segall GM. A mathematical model for the distribution of fluorodeoxyglucose in humans. J Nucl Med. 1999;40(8):1358–66.PubMed Hays MT, Segall GM. A mathematical model for the distribution of fluorodeoxyglucose in humans. J Nucl Med. 1999;40(8):1358–66.PubMed
34.
go back to reference ICRP Publication 110. Adult reference computational phantoms. Ann ICRP. 2009:39(2). ICRP Publication 110. Adult reference computational phantoms. Ann ICRP. 2009:39(2).
35.
go back to reference Kawrakow I, Rogers DWO. The EGSnrc code system: Monte Carlo simulation of electron and photon transport. Report PIRS–701. Ottawa, Canada: National Research Council of Canada; 2000. Kawrakow I, Rogers DWO. The EGSnrc code system: Monte Carlo simulation of electron and photon transport. Report PIRS–701. Ottawa, Canada: National Research Council of Canada; 2000.
36.
go back to reference Schlattl H, Zankl M, Petoussi-Henss N. Organ dose conversion coefficients for voxel models of the reference male and female from idealized photon exposures. Phys. Med. Biol. 2007;52:2123–45.CrossRef Schlattl H, Zankl M, Petoussi-Henss N. Organ dose conversion coefficients for voxel models of the reference male and female from idealized photon exposures. Phys. Med. Biol. 2007;52:2123–45.CrossRef
37.
go back to reference ICRP Publication 107. Nuclear decay data for dosimetric calculations. Annals of the ICRP. 2008;38(3). ICRP Publication 107. Nuclear decay data for dosimetric calculations. Annals of the ICRP. 2008;38(3).
38.
go back to reference Andrievski A, Wilkins RC. The response of gamma-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures. Int J Radiat Biol. 2009;85(4):369–76.CrossRef Andrievski A, Wilkins RC. The response of gamma-H2AX in human lymphocytes and lymphocytes subsets measured in whole blood cultures. Int J Radiat Biol. 2009;85(4):369–76.CrossRef
Metadata
Title
Double-strand breaks in lymphocyte DNA of humans exposed to [18F]fluorodeoxyglucose and the static magnetic field in PET/MRI
Authors
Gunnar Brix
Elisabeth Günther
Ute Rössler
David Endesfelder
Alexandra Kamp
Ambros Beer
Matthias Eiber
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
EJNMMI Research / Issue 1/2020
Electronic ISSN: 2191-219X
DOI
https://doi.org/10.1186/s13550-020-00625-1

Other articles of this Issue 1/2020

EJNMMI Research 1/2020 Go to the issue