Lesion Absorbed Dose–Response Relationship in Patients with Metastatic Castration-Resistant Prostate Cancer Undergoing [177Lu]Lu-PSMA-617 Radiopharmaceutical Therapy

The relationship between lesion absorbed dose (AD) and response in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy (RPT) remains poorly understood. The objective of this work was to investigate the AD-response relationship at both the patient and lesion levels. Methods: Sixty-five patients underwent serial SPECT/CT imaging after receiving 7.31 ± 0.27 GBq of [177Lu]Lu-PSMA-617. Single-time-point (STP) (Hänscheid approximation at 72 h) and multiple-time-point voxelwise dosimetry were performed. Patient response was evaluated by changes in serum prostate-specific antigen level before and after cycle 1 of RPT. The response of individual lesions was evaluated by the change in the SUVmax before, during, and after RPT with [68Ga]Ga-PSMA-11 PET/CT. Results: Baseline PET and SPECT lesion SUVmax were strongly correlated (Pearson r, 0.74; n = 1364 lesions). Kidney ADs were relatively low (0.28 ± 0.12 Gy/GBq). No significant decrease in estimated glomerular filtration rate was observed 1 y after RPT. On average, STP dosimetry underestimated the AD by 8%. A moderate negative relationship was observed between the mean lesion AD for an individual patient (Spearman ρ, -0.33; n = 63) and lesion (Spearman ρ, -0.30; n = 681) responses. Patients receiving a higher mean AD (>7.5 Gy) had a significantly better prostate-specific antigen response (median, 70% vs. -5%; P < 0.001; unpaired t test) and longer biochemical progression-free survival (median, 4.1 mo vs. 1.6 mo; P = 0.005; unpaired t test) compared with patients whose mean AD was less than 7.5 Gy, respectively. Conclusion: A moderate AD-response relationship was observed in patients with metastatic castration-resistant prostate cancer undergoing [177Lu]Lu-PSMA-617 RPT. The feasibility of STP dosimetry facilitates its implementation for treatment personalization. Kidney ADs may be reduced with abundant hydration.