Nuklearmedizin 2022; 61(02): 158
DOI: 10.1055/s-0042-1746002
Abstracts | NuklearMedizin 2022
WIS-Vortrag
Dosimetrie und Strahlenbiologie

DNA damage response of ultra-low dose Ra-223-exposed peripheral blood mononuclear cells

L. Göring
1   University Hospital Würzburg, Department of Nuclear Medicine, Würzburg
,
H. Scherthan
2   Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich
,
J. Müller
2   Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich
,
S. Schumann
1   University Hospital Würzburg, Department of Nuclear Medicine, Würzburg
,
A.K. Buck
1   University Hospital Würzburg, Department of Nuclear Medicine, Würzburg
,
M. Port
2   Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich
,
M. Lassmann
1   University Hospital Würzburg, Department of Nuclear Medicine, Würzburg
,
U. Eberlein
1   University Hospital Würzburg, Department of Nuclear Medicine, Würzburg
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    Ziel/Aim The aim of this study was to investigate differences in α-particle induced DNA damage after low (<100mGy) and ultra-low dose (<20mGy) internal ex vivo irradiation with Ra-223. Therefore, α-particle induced DNA damage tracks in peripheral blood mononuclear cells (PBMCs) from irradiated whole blood samples were evaluated.

    Methodik/Methods Blood samples of 10 healthy volunteers were investigated at 18 separate time points. Every sample was divided in five aliquots of which one served as non-irradiated baseline. The remaining blood samples were incubated for 1h with different Ra-223 activities to achieve nominal absorbed doses to the blood between 1mGy and 100mGy. Following internal exposure, the PBMCs were isolated from the radioactive blood samples and fixed with ethanol. The samples’ activity was determined using a calibrated germanium detector.

    Immunostaining of DNA double-strand break markers γ-H2AX and 53BP1 was used to reveal DNA damage tracks along α-particle trajectories (α-tracks) in the PBMCs’ nuclei. α-tracks were enumerated microscopically in 500 nuclei per sample.

    For evaluating differences between low and ultra-low dose irradiation, the respective track counts were normalized to the absorbed dose.

    Ergebnisse/Results 38 ultra-low dose (<20mGy) and 34 low dose (>20mGy) samples were evaluated. The normalized α-track counts for each group were normally distributed with mean values of (0.18±0.09)mGy-1 per 100 cells (ultra-low dose) and (0.15±0.03)mGy-1 per 100 cells (low dose). No significant differences (p<0.05) were observed.

    Schlussfolgerungen/Conclusions Even for absorbed doses as low as 1mGy α-tracks can be quantified with the γ-H2AX assay. The results of α-track induction after ultra-low dose internal irradiation match the findings for absorbed dose ranges between 20mGy and 100mGy.

    In comparison, in vivo data after therapy with Ra-223 showed higher average frequencies of α-tracks at similar absorbed doses, which likely reflects the different blood irradiation modalities during systemic and ex vivo blood exposure to Ra-223.


     

    Publication History

    Article published online:
    14 April 2022

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