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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 27-06-2022 | Original Article

Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with ²²³Ra

Authors: Lukas Göring, Sarah Schumann, Jessica Müller, Andreas K. Buck, Matthias Port, Michael Lassmann, Harry Scherthan, Uta Eberlein

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2022

Abstract

Purpose

As α-emitters for radiopharmaceutical therapies are administered systemically by intravenous injection, blood will be irradiated by α-particles that induce clustered DNA double-strand breaks (DSBs). Here, we investigated the induction and repair of DSB damage in peripheral blood mononuclear cells (PBMCs) as a function of the absorbed dose to the blood following internal ex vivo irradiation with [²²³Ra]RaCl₂.

Methods

Blood samples of ten volunteers were irradiated by adding [²²³Ra]RaCl₂ solution with different activity concentrations resulting in absorbed doses to the blood of 3 mGy, 25 mGy, 50 mGy and 100 mGy. PBMCs were isolated, divided in three parts and either fixed directly (d-samples) or after 4 h or 24 h culture. After immunostaining, the induced γ-H2AX α-tracks were counted. The time-dependent decrease in α-track frequency was described with a model assuming a repair rate R and a fraction of non-repairable damage Q.

Results

For 25 mGy, 50 mGy and 100 mGy, the numbers of α-tracks were significantly increased compared to baseline at all time points. Compared to the corresponding d-samples, the α-track frequency decreased significantly after 4 h and after 24 h. The repair rates R were (0.24 ± 0.05) h⁻¹ for 25 mGy, (0.16 ± 0.04) h⁻¹ for 50 mGy and (0.13 ± 0.02) h⁻¹ for 100 mGy, suggesting faster repair at lower absorbed doses, while Q-values were similar.

Conclusion

The results obtained suggest that induction and repair of the DSB damage depend on the absorbed dose to the blood. Repair rates were similar to what has been observed for irradiation with low linear energy transfer.

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Title: Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with 223Ra
Authors: Lukas Göring
Sarah Schumann
Jessica Müller
Andreas K. Buck
Matthias Port
Michael Lassmann
Harry Scherthan
Uta Eberlein
Publication date: 27-06-2022
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-022-05860-3

At a glance: The STEP trials

Springer Medicine

Repair of α-particle-induced DNA damage in peripheral blood mononuclear cells after internal ex vivo irradiation with ²²³Ra

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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