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27.04.2019 | Original Article | Ausgabe 8/2019 Open Access

European Journal of Nuclear Medicine and Molecular Imaging 8/2019

DNA damage in blood leucocytes of prostate cancer patients during therapy with 177Lu-PSMA

Zeitschrift:
European Journal of Nuclear Medicine and Molecular Imaging > Ausgabe 8/2019
Autoren:
Sarah Schumann, Harry Scherthan, Constantin Lapa, Sebastian Serfling, Razan Muhtadi, Michael Lassmann, Uta Eberlein
Wichtige Hinweise

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Abstract

Purpose

The aim of this study was to investigate the time- and dose-dependency of DNA double-strand break (DSB) induction and repair in peripheral blood leucocytes of prostate cancer patients during therapy with 177Lu-PSMA.

Methods

Blood samples from 16 prostate cancer patients receiving their first 177Lu-PSMA therapy were taken before and at seven time-points (between 1 h and 96 h) after radionuclide administration. Absorbed doses to the blood were calculated using integrated time–activity curves of the blood and the whole-body. For DSB quantification, leucocytes were isolated, fixed in ethanol and immunostained with γ-H2AX and 53BP1 antibodies. Colocalizing foci of both DSB markers were manually counted in a fluorescence microscope.

Results

The average number of radiation-induced foci (RIF) per cell increased within the first 4 h after administration, followed by a decrease indicating DNA repair. The number of RIF during the first 2.6 h correlated linearly with the absorbed dose to the blood (R2 = 0.58), in good agreement with previously published in-vitro data. At late time-points (48 h and 96 h after administration), the number of RIF correlated linearly with the absorbed dose rate (R2 = 0.56). In most patients, DNA DSBs were repaired effectively. However, in some patients RIF did not disappear completely even 96 h after administration.

Conclusion

The general pattern of the time- and dose-dependent induction and disappearance of RIF during 177Lu-PSMA therapy is similar to that of other radionuclide therapies.

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