Background <p>In this case study, we share our experience on the treatment of a patient with [¹⁷⁷Lu]Lu-PSMA for metastatic castration-resistant prostate cancer and comorbid kidney failure. Since a poor kidney function impacts [¹⁷⁷Lu]Lu-PSMA clearance, the aim of this study was to carefully monitor the radiation dose to the organs-at-risk, and measure the activity distribution during hemodialysis sessions, by imaging, blood sampling and dialysate sampling.</p> Case presentation <p>A 72-year-old patient received a total of five cycles of approximately 7.4 GBq [¹⁷⁷Lu]Lu-PSMA-I&amp;T, with an interval of 5–7 weeks per cycle. The radiation dose per cycle (mean ± SD) was measured for different regions: total body 0.51 ± 0.06&#xa0;Gy, liver (incl. tumours) 5.6 ± 0.5&#xa0;Gy, kidney (single, poor function) 3.3 ± 0.4&#xa0;Gy, salivary glands 5.5 ± 0.7&#xa0;Gy, and bone marrow 0.41 ± 0.07&#xa0;Gy.&#xa0;Hemodialysis was continued three times a week. Precautions for radiation protection were taken for the first hemodialysis session 20&#xa0;h after [¹⁷⁷Lu]Lu-PSMA administration, which took place at the radioligand therapy nursery unit. Blood and dialysate samples, collected during hemodialysis, showed a drop of the activity concentration in the blood of the patient (32% in 3&#xa0;h), and a partial return of activity to the blood (rebound effect) after the end of the hemodialysis treatment.&#xa0;The radiation dose to the bone marrow of the hemodialysis patient was elevated (by a factor of two as compared to literature), but stayed below dose thresholds for severe deterministic side effects.</p> Conclusions <p>Despite the preexisting kidney failure of a hemodialysis patient, the carefully monitored radiation dose of [¹⁷⁷Lu]Lu-PSMA therapy remained below safe dose thresholds and no signs of severe hematotoxicity were observed. </p>