Fig. 4.

Low DDR-marker levels are associated with treatment failure. Baseline [¹⁸F]F-PSMA-1007 PET/CT (maximum intensity projection (MIP), a) of a patient prior to treatment. This patient had multiple tumor lesions in lymph nodes and the skeleton, e.g., in the11^th thoracic vertebral body. Averaged SUV_max was 18.39 (above median, indicative of no progressive disease). Pretherapeutic PSA was 59 µg/l. Fluorescence microscopy images (63 × objective lens at 1.6 × magnification), with one merged and three separate channels for γ-H2AX (red), 53BP1 (green), and DAPI for nuclei stain (blue) of DDR-markers in PBLs prior to treatment (b). This patient demonstrated a low number of γ-H2AX (n = 0.16) and 53BP1 (n = 0.18) foci per cell, presumably reflecting low radiosensitivity. This patient had progressive disease after 2 cycles of [¹⁷⁷Lu]Lu-PSMA RLT (c; PET: 71 days after study inclusion, multiple new lesions (red arrows) on follow-up PET/CT; PSA: 65 days after study inclusion, + 67% compared to baseline)