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Induction and repair of DNA double-strand breaks in blood lymphocytes of patients undergoing 18F-FDG PET/CT examinations

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The purpose of this study was to evaluate DNA double-strand breaks (DSBs) in blood lymphocytes of patients undergoing positron emission tomography (PET)/CT using γ-H2AX immunofluorescence microscopy and to differentiate between 18F-fluorodeoxyglucose (FDG) and CT-induced DNA lesions.

Methods

This study was approved by the local Ethics Committee and complies with Health Insurance Portability and Accountability Act (HIPAA) requirements. After written informed consent was obtained, 33 patients underwent whole-body 18F-FDG PET/CT (3 MBq/kg body weight, 170/100 reference mAs at 120 kV). The FDG PET and CT portions were performed as an initial CT immediately followed by the PET. Blood samples were obtained before, at various time points following 18F-FDG application and up to 24 h after the CT scan. Distinct foci representing DSBs were quantified in isolated lymphocytes using fluorescence microscopy after staining against the phosphorylated histone variant γ-H2AX.

Results

The DSB values at the various time points were significantly different (p < 0.001). The median baseline level was 0.08/cell (range 0.06–0.12/cell). Peaks of radiation-induced DSBs were found 30 min after 18F-FDG administration (median excess foci 0.11/cell, range 0.06–0.27/cell) and 5 min after CT (median excess foci 0.17/cell, range 0.05–0.54/cell). A significant correlation between CT-induced DSBs and dose length product was obtained (ρ = 0.898, p < 0.001). After 24 h DSB values were still slightly but significantly elevated (median foci 0.11/cell, range 0.10–0.14/cell, p = 0.003) compared to pre-exposure levels.

Conclusion

PET/CT-induced DSBs can be monitored using γ-H2AX immunofluorescence microscopy. Peak values may be obtained 30 min after 18F-FDG injection and 5 min after CT. The radionuclide contributes considerably to the total DSB induction in this setting.

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Acknowledgments

We thank Christina Engert, Tobias Löwe, Matthias Sommer, Bernhard Schmidt and Wolfram Nitsch for excellent technical assistance and Luitpold Distel for extraordinary collaboration in the lab. We also thank Ulrich Kahl, Ulrich Gärtner, Gerson Schütze, Kilian Bose, Rainer Linke and Roland Wondra for their support in patient examination and acquisition of blood samples.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Radiology, University Hospital Erlangen, Erlangen, Germany

    Matthias S. May, Michael Brand, Wolfgang Wuest, Katharina Anders, Michael Uder & Michael A. Kuefner

  2. Department of Nuclear Medicine, University Hospital Erlangen, Erlangen, Germany

    Torsten Kuwert, Olaf Prante, Daniela Schmidt & Simone Maschauer

  3. Department of Radiology, University of North Carolina, Chapel Hill, NC, USA

    Richard C. Semelka

  4. Department of Radiology, University Hospital Erlangen, Maximiliansplatz 1, 91054, Erlangen, Germany

    Matthias S. May

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  1. Matthias S. May
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Correspondence to Matthias S. May.

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May, M.S., 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 39, 1712–1719 (2012). https://doi.org/10.1007/s00259-012-2201-1

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  • DOI: https://doi.org/10.1007/s00259-012-2201-1

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