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DNA double-strand breaks in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy

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Abstract

Objectives

To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with 99mTc activity in blood samples.

Methods

Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections. 99mTc activity was measured in each blood sample. For immunofluorescence microscopy, distinct foci representing DSBs were quantified in lymphocytes after staining for the phosphorylated histone variant y-H2AX.

Results

The 99mTc-MIBI activity measured on days one and two was similar (254±25 and 258±27 MBq; p=0.594). Compared with baseline DSB foci (0.09±0.05/cell), a significant increase was found at 5min (0.19±0.04/cell) and 1h (0.18±0.04/cell) after the first injection and at 5min and 1h after the second injection (0.21±0.03 and 0.19±0.04/cell, respectively; p=0.003 for both). At 24h after the first and second injections, the number of DSB foci had returned to baseline (0.06±0.02 and 0.12±0.05/cell, respectively). 99mTc activity levels in peripheral blood samples correlated well with DSB counts (r=0.451).

Conclusions

DSB counts reflect 99mTc-MIBI activity after injection for two-day MPS, and might allow individual monitoring of biological effects of cardiac nuclear imaging.

Key Points

• Myocardial perfusion scintigraphy using 99mTc induces time-dependent double-strand breaks (DSBs)

• γ-H2AX immunofluorescence microscopy shows DSB as an early response to radiotracer injection

• Activity measurements of 99mTc correlate well with detected DSB

• DSB foci induced by 99mTc return to baseline 24h after radiotracer injection

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Abbreviations

99mTc:

Technetium 99m

Cpm:

Counts per minute

DNA:

Deoxyribonucleic acid

SB:

Double-strand break

FCS:

Foetal calf serum

MBq:

Megabecquerel

MIBI:

Methoxy-isobutyl-isonitrile

MPI:

Myocardial perfusion imaging

MPS:

Myocardial perfusion scintigraphy

MRI:

Magnetic resonance imaging

RPMI:

Roswell Park Memorial Institute

γ-H2AX:

Gamma-H2AX protein, human

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Funding

Prof. Dewey has received grant support for the current study (DE 1361/14-1). The multicentre CORE-320 study was supported by a grant from Toshiba Medical Systems. The authors state that this work has not received any industry funding.

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Authors and Affiliations

  1. Department of Radiology, Charité – Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Matthias Rief, Lisa Hartmann, Dominik Geisel, Felicitas Richter, Winfried Brenner & Marc Dewey

  2. Humboldt-Universität zu Berlin, Berlin, Germany

    Matthias Rief, Lisa Hartmann, Dominik Geisel, Felicitas Richter, Winfried Brenner & Marc Dewey

  3. Freie Universität Berlin, Berlin, Germany

    Matthias Rief, Lisa Hartmann, Dominik Geisel, Felicitas Richter, Winfried Brenner & Marc Dewey

Authors
  1. Matthias Rief
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  2. Lisa Hartmann
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  3. Dominik Geisel
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  4. Felicitas Richter
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  5. Winfried Brenner
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  6. Marc Dewey
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Corresponding author

Correspondence to Marc Dewey.

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Guarantor

The scientific guarantor of this publication is Prof. Dewey.

Conflict of interest

The authors of this manuscript declare relationships with the following companies.

Prof. Dewey has received grant support for the current study (DE 1361/14-1), the FP7 Program of the European Commission for the randomised multicentre DISCHARGE trial (603266-2, HEALTH-2012.2.4.-2), the European Regional Development Fund (20072013 2/05, 20072013 2/48), the German Heart Foundation/German Foundation of Heart Research (F/23/08, F/27/10), the Joint Program of the German Research Foundation (DFG) and the German Federal Ministry of Education and Research (BMBF) for meta-analyses (01KG1013, 01KG1110, 01KG1110), GE Healthcare, Bracco, Guerbet, and Toshiba Medical Systems. Prof. Dewey has received lecture fees from Toshiba Medical Systems, Guerbet, Cardiac MR Academy Berlin, and Bayer (Schering-Berlex). Prof. Dewey is a consultant to Guerbet and one of the principal investigators of multicentre studies (CORE-64 and 320) on coronary CT angiography sponsored by Toshiba Medical Systems. He is also the editor of Coronary CT Angiography and Cardiac CT, both published by Springer, and offers hands-on workshops on cardiovascular imaging (www.ct-kurs.de). Prof. Dewey is an associate editor of Radiology and European Radiology. Institutional master research agreements exist with Siemens Medical Solutions, Philips Medical Systems and Toshiba Medical Systems. The terms of these arrangements are managed by the legal department of Charité – Universitätsmedizin Berlin.

All other authors: None.

Statistics and biometry

No complex statistical methods were necessary for this paper.

Ethical approval

Institutional Review Board approval was obtained.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Methodology

• prospective

• clinical study

• performed at one institution

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Rief, M., Hartmann, L., Geisel, D. et al. DNA double-strand breaks in blood lymphocytes induced by two-day 99mTc-MIBI myocardial perfusion scintigraphy. Eur Radiol 28, 3075–3081 (2018). https://doi.org/10.1007/s00330-017-5239-4

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  • DOI: https://doi.org/10.1007/s00330-017-5239-4

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