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Purpose <p>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).</p> Methods <p>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.</p> Results <p>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], <i>p</i> &lt; 0.05) and haemoglobin (0.29 [0.41] vs. 0.092 [0.20], <i>p</i> = 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&#xa0;Gy and 18.1&#xa0;Gy for TMTAD(C1) and at 11.3&#xa0;Gy and 31.7&#xa0;Gy for TMTAD(C1-C4).</p> Conclusion <p>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.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年3月7日

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  • Arnaud Dieudonné,
  • Aya Terro,
  • Arthur Dumouchel,
  • Solène Perret,
  • Adrien Pommier,
  • Agathe Edet-Sanson,
  • Pierre Vera,
  • Frédéric Di Fiore,
  • Laetitia Augusto,
  • Pierre Decazes,
  • David Tonnelet

摘要

Purpose

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).

Methods

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.

Results

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).

Conclusion

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.

Graphical abstract