Clinical value of per-treatment whole-body single-time-point automated dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 therapy in metastatic castration-resistant prostate cancer.

Abstract

To assess the clinical value of single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 radioligand therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). Fifty-nine patients with progressive mCRPC expressing PSMA and previously treated with androgen receptor pathway inhibitors and taxane-based chemotherapy were retrospectively analysed. SPECT/CT imaging was performed after the first (C1) and fourth (C4) [¹⁷⁷Lu]Lu-PSMA-617 infusions on 360°-CZT camera. Automated segmentation and dosimetry protocols were applied to quantify absorbed doses in bone marrow and lesions. Dose-effect relationships were assessed using blood counts, PSA responses (PSA50 criteria), and PET imaging. Statistical analyses included Spearman correlation, Wilcoxon signed-rank test, and logistic regression. Bone marrow absorbed dose (BMAD) at C1 was significantly correlated with red blood cells (RBC, ρ = -0.3) and haemoglobin (ρ = -0.26) decline. A higher BMAD was associated with greater declines in RBC count (median [IQR] 0.31 [0.33] Gy vs. 0.076 [0.19], p < 0.05) and haemoglobin (0.29 [0.41] vs. 0.092 [0.20], p = 0.056). A moderate negative correlation was found between PSA variation and total metastatic tumour absorbed (TMTAD) dose at C1 (ρ = -0.35) and from C1 to C4 (ρ = -0.35). Response modelling (based on PSA50) estimated 50% and 80% probabilities of response at 8.8 Gy and 18.1 Gy for TMTAD(C1) and at 11.3 Gy and 31.7 Gy for TMTAD(C1-C4). Single-time-point dosimetry for [¹⁷⁷Lu]Lu-PSMA-617 therapy in mCRPC is clinically relevant, demonstrating dose-dependent haematological decline and therapeutic response. This approach has the potential to facilitate more personalised and accessible radioligand therapy.