Abstract
Background: DNA double-strand breaks (DSBs) in cells of radionuclide-treated patients are quantifiable by immunofluorescence microscopy, using phosphorylation of histone variant H2AX (γ-H2AX) to mark radiation-induced foci (RIF). Based on this method, we compared excess RIF side-by-side in recipients of lutetium 177 (177Lu)-DOTATOC or -PSMA-617 radioligands. We also examined relations between blood dose and dose rate, RIF, and platelet counts. Material and Methods: Venous blood samples were obtained from 48 patients subjected to 177Lu-labeled radioligand therapy (DOTATOC, 26; PSMA-617, 22) to quantify blood lymphocyte RIF and blood activity concentration at various time points, including baseline (prior to injection) and post injection (PI) readings (5 min, 30 min, 4 h, 24 h, 48 h, and 72 h). Absorbed doses and dose rates to blood were derived from sequentially assessed blood activity concentrations and gamma camera imaging. Platelet levels in routine blood tests were monitored for 3 days PI to assess responses. Results: RIF counts averaged 0.25 ± 0.15 at baseline. PI-RIF counts were significantly higher than baseline values, peaking at 5 min (average, 3.93 ± 2.51) and declining thereafter. Compared with RIF counts of 177Lu-DOTATOC, those of 177Lu-PSMA-617 were significantly higher at 5 min PI and significantly lower at 72 h PI. These differences could not be fully explained by blood doses and dose rates, which were significantly higher for PSMA than for DOTATOC treatment at every time point. RIF counts overall correlated with dose rates across all time points (Pearson’s r=0.78; p<0.01) and with absorbed dose until 4 h PI only (Pearson’s r=0.42; p<0.01). Declines in platelet concentration correlated significantly with RIFs at 72 h PI (Pearson’s r=-0.34; p<0.05). Conclusion: Although values generated by the currently used blood dosimetry model correlated with RIF counts, the difference observed in DOTATOC and PSMA treatment groups was unexplained. Significantly more RIFs were found in 177Lu-DOTATOC recipients by comparison, despite lower dose rates and blood doses, exposing a potential limitation.
- Radiobiology/Dosimetry
- Radionuclide Therapy
- γ-H2AX
- 177Lu-labeled therapy
- DOTATOC
- PSMA
- radiation-induced foci
- Copyright © 2020 by the Society of Nuclear Medicine and Molecular Imaging, Inc.