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European Radiology Experimental

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Open Access 01-12-2018 | Original article

The potential toxic impact of different gadolinium-based contrast agents combined with 7-T MRI on isolated human lymphocytes

Authors: Björn Friebe, Frank Godenschweger, Mahsa Fatahi, Oliver Speck, Dirk Roggenbuck, Dirk Reinhold, Annika Reddig

Published in: European Radiology Experimental | Issue 1/2018

Abstract

Background

To investigate a potentially amplifying genotoxic or cytotoxic effect of different gadolinium-based contrast agents (GBCAs) in combination with ultra-high-field 7-T magnetic resonance imaging (MRI) exposure in separated human peripheral blood lymphocytes.

Methods

This in vitro study was approved by the local ethics committee and written informed consent was obtained from all participants. Isolated lymphocytes from twelve healthy donors were incubated with gadobutrol, gadoterate meglumine, gadodiamide, gadopentetate dimeglumine, or gadoxetate either alone or combined with 7-T MRI (1 h). Deoxyribonucleic acid (DNA) double-strand breaks were assessed 15 min after MRI exposure by automated γH2AX foci quantification. Cytotoxicity was determined at later endpoints by Annexin V/propidium iodide apoptosis assay (24 h) and [³H]-thymidine proliferation test (72 h). As a reference, lymphocytes from four different donors were exposed analogously to iodinated contrast agents (iomeprol, iopromide) in combination with computed tomography.

Results

Baseline γH2AX levels (0.08 ± 0.02 foci/cell) were not significantly (p between 0.135 and 1.000) enhanced after administration of GBCAs regardless of MRI exposure. In contrast to the two investigated macrocyclic GBCAs, lymphocytes exposed to the three linear GBCAs showed a dose-dependent increase in apoptosis (maximum 186% of unexposed control, p < 0.001) and reduced proliferation rate (minimum 0.7% of unexposed control, p < 0.001). However, additional 7-T MRI co-exposure did not alter GBCA-induced cytotoxicity.

Conclusions

Exposure of lymphocytes to different GBCAs did not reveal significant induction of γH2AX foci, and enhanced cytotoxicity was only observed in lymphocytes treated with the linear GBCAs used in this study, independent of additional 7-T MRI co-exposure.

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OECD (2014) 46. Magnetic resonance imaging (MRI) exams, total per 1000 population. https://doi.org/10.1787/mri-exam-total-table-2014-1-en

Grand View Research Inc. (2017) Magnetic resonance imaging (MRI) market analysis by architecture (open and closed), by field strength (low, medium, high), by application (brain & neurological, spine & musculoskeletal, vascular, abdominal & pelvic, cardiac, breast), and segment forecasts. http://www.grandviewresearch.com/industry-analysis/magnetic-resonance-imaging-market

Wang Y, Alkasab TK, Narin O et al (2011) Incidence of nephrogenic systemic fibrosis after adoption of restrictive gadolinium-based contrast agent guidelines. Radiology 260:105–111CrossRef

Kanda T, Ishii K, Kawaguchi H, Kitajima K, Takenaka D (2014) High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material. Radiology 270:834–841CrossRef

Rogosnitzky M, Branch S (2016) Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms. BioMetals 29:365–76CrossRef

Radbruch A, Haase R, Kieslich PJ et al (2017) No signal intensity increase in the dentate nucleus on unenhanced T1-weighted MR images after more than 20 serial injections of macrocyclic gadolinium-based contrast agents. Radiology 282:699–707CrossRef

Vijayalaxmi, Fatahi M, Speck O (2015) Magnetic resonance imaging (MRI): A review of genetic damage investigations. Mutat Res Rev Mutat Res 764:51–63CrossRef

Hill MA, O’Neill P, McKenna WG (2016) Comments on potential health effects of MRI-induced DNA lesions: quality is more important to consider than quantity. Eur Heart J Cardiovasc Imaging 17:1230–1238CrossRef

Foster KR, Moulder JE, Budinger TF (2017) Will an MRI examination damage your genes? Radiat Res 187:1–6CrossRef

10.

Fatahi M, Reddig A, Friebe B, Reinhold D, Speck O (2017) MRI and genetic damage: an update. Curr Radiol Rep 5:20

11.

Simi S, Ballardin M, Casella M et al (2008) Is the genotoxic effect of magnetic resonance negligible? Low persistence of micronucleus frequency in lymphocytes of individuals after cardiac scan. Mutat Res 645:39–43CrossRef

12.

Lee JW, Kim MS, Kim YJ, Choi YJ, Lee Y, Chung HW (2011) Genotoxic effects of 3 T magnetic resonance imaging in cultured human lymphocytes. Bioelectromagnetics 32:535–542CrossRef

13.

Fiechter M, Stehli J, Fuchs TA, Dougoud S, Gaemperli O, Kaufmann PA (2013) Impact of cardiac magnetic resonance imaging on human lymphocyte DNA integrity. Eur Heart J 34:2340–2345CrossRef

14.

Lancellotti P, Nchimi A, Delierneux C et al (2015) Biological effects of cardiac magnetic resonance on human blood cells. Circ Cardiovasc Imaging 8:e003697CrossRef

15.

Szerencsi Á, Kubinyi G, Váliczkó É et al (2013) DNA integrity of human leukocytes after magnetic resonance imaging. Int J Radiat Biol 89:870–876CrossRef

16.

Brand M, Ellmann S, Sommer M et al (2015) Influence of cardiac MR imaging on DNA double-strand breaks in human blood lymphocytes. Radiology 277:406–412CrossRef

17.

Reddig A, Fatahi M, Friebe B et al (2015) Analysis of DNA double-strand breaks and cytotoxicity after 7 tesla magnetic resonance imaging of isolated human lymphocytes. PLoS One 10:e0132702CrossRef

18.

Fatahi M, Reddig A, Vijayalaxmi et al (2016) DNA double-strand breaks and micronuclei in human blood lymphocytes after repeated whole body exposures to 7T magnetic resonance imaging. Neuroimage 133:288–293CrossRef

19.

Reddig A, Fatahi M, Roggenbuck D et al (2017) Impact of in vivo high-field-strength and ultra-high-field-strength MR imaging on DNA double-strand-break formation in human lymphocytes. Radiology 282:782–789CrossRef

20.

Grudzenski S, Kuefner MA, Heckmann MB, Uder M, Löbrich M (2009) Contrast medium-enhanced radiation damage caused by CT examinations. Radiology 253:706–714CrossRef

21.

Pathe C, Eble K, Schmitz-Beuting D et al (2011) The presence of iodinated contrast agents amplifies DNA radiation damage in computed tomography. Contrast Media Mol Imaging 6:507–513CrossRef

22.

Piechowiak EI, Peter JF, Kleb B, Klose KJ, Heverhagen JT (2015) Intravenous iodinated contrast agents amplify DNA radiation damage at CT. Radiology 275:692–697CrossRef

23.

Jost G, Golfier S, Pietsch H et al (2009) The influence of x-ray contrast agents in computed tomography on the induction of dicentrics and gamma-H2AX foci in lymphocytes of human blood samples. Phys Med Biol 54:6029–6039CrossRef

24.

Yildiz S, Cece H, Kaya I et al (2011) Impact of contrast enhanced MRI on lymphocyte DNA damage and serum visfatin level. Clin Biochem 44:975–979CrossRef

25.

Witzleb E (1987) Functions of the vascular system. In: Schmidt RF, Thews G (eds) Human Physiology, 23rd edn. Springer Berlin Heidelberg, Berlin, Heidelberg, p 490

26.

Heinrich MC, Kuhlmann MK, Kohlbacher S et al (2007) Cytotoxicity of iodinated and gadolinium-based contrast agents in renal tubular cells at angiographic concentrations: in vitro study. Radiology 242:425–434CrossRef

27.

Willitzki A, Lorenz S, Hiemann R et al (2013) Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence. Cytometry A 83:1017–1026CrossRef

28.

Schwenzer NF, Bantleon R, Maurer B et al (2007) Detection of DNA double-strand breaks using gammaH2AX after MRI exposure at 3 tesla: an in vitro study. J Magn Reson Imaging 26:1308–1314CrossRef

29.

Erdamar H, Gürgel A, Namuslu M et al (2014) Is magnetic resonance imaging really innocent? Clin Chem Lab Med 52:24114916CrossRef

30.

Cho S, Lee Y, Lee S, Choi YJ, Chung HW (2014) Enhanced cytotoxic and genotoxic effects of gadolinium following ELF-EMF irradiation in human lymphocytes. Drug Chem Toxicol 37:440–447CrossRef

31.

Aime S, Caravan P (2009) Biodistribution of gadolinium-based contrast agents, including gadolinium deposition. J Magn Reson Imaging 30:1259–1267CrossRef

32.

Caschera L, Lazzara A, Piergallini L, Ricci D, Tuscano B, Vanzulli A (2016) Contrast agents in diagnostic imaging: Present and future. Pharmacol Res 110:65–75CrossRef

33.

Fraum TJ, Ludwig DR, Bashir MR, Fowler KJ (2017) Gadolinium-based contrast agents: a comprehensive risk assessment. J Magn Reson Imaging 46:338–353CrossRef

34.

Frenzel T, Lengsfeld P, Schirmer H, Hütter J, Weinmann HJ (2008) Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 degrees C. Invest Radiol 43:817–828

Title: The potential toxic impact of different gadolinium-based contrast agents combined with 7-T MRI on isolated human lymphocytes
Authors: Björn Friebe
Frank Godenschweger
Mahsa Fatahi
Oliver Speck
Dirk Roggenbuck
Dirk Reinhold
Annika Reddig
Publication date: 01-12-2018
Publisher: Springer International Publishing
Published in: European Radiology Experimental / Issue 1/2018
Electronic ISSN: 2509-9280
DOI: https://doi.org/10.1186/s41747-018-0069-y

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Springer Medicine

The potential toxic impact of different gadolinium-based contrast agents combined with 7-T MRI on isolated human lymphocytes

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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