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

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; Sandy Srinivas; Andrei Iagaru

doi:10.1007/s00259-024-06718-6

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 Apr 18. doi: 10.1007/s00259-024-06718-6. Online ahead of print.

Authors

Affiliations

¹ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Drive, H2200, Stanford, CA, 94305, USA.
² Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, 94305, USA.
³ Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, 300 Pasteur Drive, H2200, Stanford, CA, 94305, USA. aiagaru@stanford.edu.

PMID: 38635050
DOI: 10.1007/s00259-024-06718-6

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), SUV_max and SUV_mean 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 SUV_max or SUV_mean 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.

Keywords: Lutetium-PSMA; Metastatic castration resistant prostate cancer; SPECT/CT; Treatment response biomarker.