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Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer

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Abstract

Purpose

Lutetium-177 [177Lu]Lu-PSMA-617 radioligand therapy (RLT) represents a significant advancement for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improvements in radiographic progression free survival (rPFS) and overall survival (OS) with a low rate of associated side effects. Currently, most post-therapy SPECT/CT is conducted at 24 h after infusion. This study examines the clinical utility of a next-generation multi-detector Cadmium-Zinc-Telluride (CZT) SPECT/CT system (StarGuide) in same-day post-infusion assessment and early treatment response to [177Lu]Lu-PSMA-617.

Methods

In this retrospective study, 68 men with progressive mCRPC treated with [177Lu]Lu-PSMA-617 at our center from June 2022 to June 2023 were evaluated. Digital whole-body SPECT/CT imaging was performed after [177Lu]Lu-PSMA-617infusion (mean ± SD: 1.8 ± 0.6 h, range 1.1–4.9 h). Quantitative analysis of [177Lu]Lu-PSMA-617 positive lesions was performed in patients who underwent at least 2 post-therapy SPECT/CT, using liver parenchyma uptake as reference. Metrics including [177Lu]Lu-PSMA-617 positive total tumor volume (Lu-TTV), SUVmax and SUVmean were calculated. These quantitative metrics on post-infusion SPECT/CT images after cycles 1, 2 and 3 were correlated with overall survival (OS), prostate specific antigen-progression free survival (PSA-PFS) as defined by prostate cancer working group 3 (PCWG3), and PSA decrease over 50% (PSA50) response rates.

Results

56 patients (means age 76.2 ± 8.1 years, range: 60–93) who underwent at least 2 post-therapy SPECT/CT were included in the image analysis. The whole-body SPECT/CT scans (~ 12 min per scan) were well tolerated, with 221 same-day scans performed (89%). At a median of 10-months follow-up, 33 (58.9%) patients achieved PSA50 after [177Lu]Lu-PSMA-617 treatment and median PSA-PFS was 5.0 months (range: 1.0–15 months) while median OS was not reached. Quantitative analysis of SPECT/CT images showed that 37 patients (66%) had > 30% reduction in Lu-TTV, associated with significantly improved overall survival (median not reached vs. 6 months, P = 0.008) and PSA-PFS (median 6 months vs. 1 months, P < 0.001). However, changes in SUVmax or SUVmean did not correlate with PSA-PFS or OS.

Conclusion

We successfully implemented same-day post-therapy SPECT/CT after [177Lu]Lu-PSMA-617 infusions. Quantitation of 1–2 h post-therapy SPECT/CT images is a promising method for assessing treatment response. However, the approach is currently limited by its suboptimal detection of small tumor lesions and the necessity of incorporating a third-cycle SPECT/CT to mitigate the effects of any potential treatment-related flare-up. Further investigation in a larger patient cohort and prospective validation is essential to confirm these findings and to explore the role of SPECT/CT as a potential adjunct to PSMA PET/CT in managing mCRPC.

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Data availability

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Authors and Affiliations

  1. Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Drive, H2200, Stanford, CA, 94305, USA

    Hong Song, Maria Isabel Leonio, Valentina Ferri, Heying Duan, Carina Mari Aparici, Guido Davidzon, Benjamin L. Franc, Farshad Moradi, Jagruti Shah & Andrei Iagaru

  2. Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, 94305, USA

    Colin P. Bergstrom, Alice C. Fan, Sumit Shah, Ali Raza Khaki & Sandy Srinivas

Authors
  1. Hong Song
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  2. Maria Isabel Leonio
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Contributions

HS content planning, data analyses, manuscript writing and editing; MIL data analyses, manuscript editing; VF data analyses, manuscript editing; HD data analyses, manuscript editing; CMA manuscript editing; GD manuscript editing; BLF manuscript editing; FM manuscript editing; JS manuscript editing; CPM manuscript editing; ACF manuscript editing; SS manuscript editing; ARK manuscript editing; SS manuscript editing; AI content planning, data analyses, manuscript editing.

Corresponding author

Correspondence to Andrei Iagaru.

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Ethical approval

All procedures performed in our study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Stanford University Institutional Review Board approved this retrospective data analysis.

Conflicts of interest

Andrei Iagaru is an Associate Editor at the European Journal of Nuclear Medicine and Molecular Imaging. Hong Song, Maria Isabel Leonio, Valentina Ferri, Heying Duan, Carina Mari Aparici, Guido Davidzon, Benjamin L. Franc, Farshad Moradi, Jagruti Shah, Colin P Bergstrom, Alice C Fan, Sumit Shah, Ali Raza Khaki and Sandy Srinivas declare that they have no conflict of interest or competing interests.

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Waived by the Stanford University Institutional Review Board for this retrospective data analysis.

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Song, H., Leonio, M.I., Ferri, V. et al. Same-day post-therapy imaging with a new generation whole-body digital SPECT/CT in assessing treatment response to [177Lu]Lu-PSMA-617 in metastatic castration-resistant prostate cancer. Eur J Nucl Med Mol Imaging (2024). https://doi.org/10.1007/s00259-024-06718-6

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