[¹⁷⁷Lu]Lu-Prostate-Specific Membrane Antigen-617 in a Patient with Metastatic Castration-Resistant Prostate Cancer and Status After Bilateral Nephrectomy

In a 79-y-old man with metastatic castration-resistant prostate cancer and a history of bilateral nephrectomy for renal cell carcinoma, undergoing thrice-weekly hemodialysis, [⁶⁸Ga]Ga-PSMA-11 PET revealed intense prostate-specific membrane antigen–avid lesions (Fig. 1A). He received 2 cycles of [¹⁷⁷Lu]Lu-PSMA-617, with a 60% dose reduction to 3.1 GBq (40% of the standard dose) in each cycle (1). Regular hemodialysis persisted throughout the treatment at specified intervals. After therapy, the patient’s prostate-specific antigen level decreased by over 90% and was sustained for 4–5 mo. However, he experienced grade 4 thrombocytopenia and severe infections, persisting for several weeks. Because of these adverse effects, [¹⁷⁷Lu]Lu-PSMA-617 was temporarily halted.

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FIGURE 1.

(A) [⁶⁸Ga]Ga-PSMA-11 PET scan showed metastases in bone (highest SUV_max, 52.27), paraaortic lymph nodes (SUV_max, 11.39), pelvic lymph nodes (SUV_max, 26.82), left adrenal gland (SUX_max, 44.30), and lower right lung (SUV_max, 7.86), as well as physiologic uptake in bowels (arrow). (B) Time–activity curve and protocol of administration, hemodialysis, and pharmacokinetic measurements.

In the second cycle, we assessed whole-body and excreted activity and biologic effective half-life by an indirect approach involving the measurement of residual activity in the patient’s body at 4 distinct time points using a γ-camera (Symbia T; Siemens Healthineers) (1). The decay-corrected residual activity was 45.1% at 144 h after infusion, with the last hemodialysis session conducted 99–102 h after infusion. The whole-body effective half-life was 108.3 h (Fig. 1B).

In this patient, a 60% dose reduction, the lowest documented in the literature (2,3), resulted in unexpected bone marrow toxicity. Additionally, the observed effective half-life and residual activity exceeded previous findings in patients with normal renal function (1), suggesting delayed clearance of [¹⁷⁷Lu]Lu-PSMA-617 in this hemodialysis patient.

• © 2024 by the Society of Nuclear Medicine and Molecular Imaging.

• Received for publication January 30, 2024.
• Accepted for publication April 10, 2024.