AccScience Publishing / ARNM / Online First / DOI: 10.36922/ARNM025110011
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ORIGINAL RESEARCH ARTICLE

Identifying lutetium-177 prostate-specific membrane antigen-617 treatment response patterns using a quantitative prostate-specific membrane antigen positron emission tomography/computed tomography traffic light workflow within the LuPIN trial

Sarennya Pathmanandavel1,2* ,  Megan Crumbaker1,2,3,4 ,  Andrew Nguyen1,4 ,  Andrew O. Yam2,3,4,5 ,  Peter Wilson6 ,  Remy Niman6 ,  Maria Ayers1 ,  Shikha Sharma1 ,  Peter Eu7 ,  Andrew J. Martin8 ,  Martin R. Stockler8 ,  Anthony M. Joshua2,3,4,9 ,  Louise Emmett1,3,4,9
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1 Department of Theranostics and Nuclear Medicine, St Vincent’s Hospital, Sydney, New South Wales, Australia
2 The Kinghorn Cancer Centre, St Vincent’s Hospital, Sydney, New South Wales, Australia
3 Garvan Institute of Medical Research, Sydney, New South Wales, Australia
4 St. Vincent’s Clinical School, University of New South Wales, Sydney, New South Wales, Australia
5 School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, New South Wales, Australia
6 MIM Software Inc., Cleveland, Ohio, United States of America
7 Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
8 NHMRC Clinical Trials Centre, University of Sydney, Sydney, New South Wales, Australia
9 Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia
ARNM, 025110011 https://doi.org/10.36922/ARNM025110011
Received: 14 March 2025 | Revised: 8 July 2025 | Accepted: 22 July 2025 | Published online: 5 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) improves survival in metastatic castration-resistant prostate cancer, but more optimal tools are needed for therapeutic response assessment and early detection of resistance. We evaluated a quantitative imaging workflow using prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography to measure lesional changes following 177Lu-PSMA-617 therapy. Pre- and post-treatment gallium-68-labeled PSMA-11 PET scans from the trial were analyzed using a novel traffic light workflow (TLW), assessing lesion-specific changes in tumor volume and maximum standardized uptake value in men treated with up to six cycles of 177Lu-PSMA-617 and a radiation sensitizer (NOX66). Lesions were categorized as “reducing” (≥30% volume decrease), “stable” (<30% change), or “increasing” (≥30% increase or new lesions). Overall response was classified as “responder” (no increasing/new lesions), “low-volume progressor” (<50% of total tumor volume [TTV] increasing/new lesions), or “high-volume progressor” (>50% of TTV increasing/new lesions). TLW response classifications were compared with Response Evaluation Criteria in PSMA PET (RECIP) 1.0 and correlated with overall survival (OS). Among 37 men who underwent pre- and post-treatment PET imaging, 68% (25/37) completed six cycles, 32% (12/37) received 2–5 cycles, and 70% (26/37) had a >50% prostate-specific antigen (PSA) decline. The median PSA progression-free survival (PSA-PFS) was 8.6 months; median OS was 22.0 months. At post-treatment imaging, 54% (20/37) showed progression. TLW classified 24% as “responders,” 41% as “low-volume progressors,” and 35% as “high-volume progressors.” “Responders” had longer OS than “low-volume progressors” (median 17.7 vs. 12.0 months) or “high-volume progressors” (median 7.5 months, p=0.005). RECIP 1.0 classified 24% as partial response, 51% stable disease, and 24% as progressive disease. In summary, TLW shows potential to delineate complex response patterns. Following validation in larger cohorts, TLW will inform therapeutic decision-making.

Graphical abstract
Keywords
Metastatic prostate cancer
Theranostics
Lutetium-prostate-specific membrane antigen
Therapeutic response
Funding
The investigator-initiated study was sponsored by St Vincent’s Hospital and supported by a Cancer Institute NSW prostate translational research grant. Noxopharm Limited provided funding for the drug and PET scans, whereas AAA/Novartis provided the PSMA-617 ligand.
Conflict of interest
Louise Emmett holds an advisory position at Clarity Pharmaceuticals and receives trial support from Novartis and Astellas and grant funding from the St Vincent’s Clinic Foundation. Anthony M. Joshua holds an advisory position at Noxopharm Limited and receives institutional research funding from Novartis. Remy Niman and Peter Wilson are salaried employees of MIM Software Inc. All other authors declare no relevant conflicts of interest.
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Advances in Radiotherapy & Nuclear Medicine, Electronic ISSN: 2972-4392 Print ISSN: 3060-8554, Published by AccScience Publishing
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