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.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2025 Oct 01*** epublish ***
Milan Grkovski, Simone S Krebs, Joseph A O'Donoghue, Jonathan Kuten, Audrey Mauguen, Parnian Shobeiri, Daniel Lafontaine, Maria Thor, Finn Augensen, Josef J Fox, Neeta Pandit-Taskar, Mark P Dunphy, Lisa Bodei, John L Humm, Heiko Schöder
Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York; ., Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York., Department of Epidemiology-Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York; and., Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; .
PubMed http://www.ncbi.nlm.nih.gov/pubmed/40774698