Towards Routine AI-Based PET/CT and SPECT/CT Lesion Segmentation and Tracking in PSMA Theranostics
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Abstract
Quantitative molecular imaging is central to treatment response assessment in oncology, yet clinical practice remains largely dominated by patient-level or limited target-lesion criteria that ignore inter-lesion heterogeneity. This limitation is particularly important in prostate cancer, where PSMA PET/CT can reveal extensive skeletal and nodal metastatic disease that often evolves heterogeneously under therapy. Accurate and scalable lesion segmentation and tracking across serial PSMA PET/CT and post-therapy SPECT/CT scans is therefore essential for implementing emerging PSMA-specific response frameworks, such as RECIP 1.0, and for enabling lesion-level dosimetry in 177Lu-PSMA radiopharmaceutical therapies (RPTs).
This article examines clinical motivations, technical foundations, and future pathways for automated lesion tracking in prostate cancer imaging. We focus on the unique requirements introduced by PSMA PET/CT compared with FDG PET/CT and highlight the critical role of quantitative SPECT/CT in linking imaging-derived disease characterization with delivered therapeutic dose. Recent advances in AI-based segmentation and automated lesion matching now make scalable longitudinal lesion correspondence feasible, providing comprehensive infrastructure for standardized response assessment and personalized PSMA-based theranostics.
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2- Humbert, O., N. Cadour, M. Paquet, R. Schiappa, M. Poudenx, D. Chardin, D. Borchiellini, D. Benisvy, M.J. Ouvrier, C. Zwarthoed, A. Schiazza, M. Ilie, H. Ghalloussi, P.M. Koulibaly, J. Darcourt, J. Otto, "18FDG PET/CT in the early assessment of non-small cell lung cancer response to immunotherapy: frequency and clinical significance of atypical evolutive patterns." European journal of nuclear medicine and molecular imaging, Vol. 47 (No. 5), pp. 1158–67, (2020).
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4- Morin, F., J.-M. Beauregard, M. Bergeron, M. Nguile Makao, L. Lacombe, V. Fradet, Y. Fradet, F. Pouliot, "Metabolic imaging of prostate cancer reveals intrapatient intermetastasis response heterogeneity to systemic therapy." European Urology Focus, Vol. 3 (No. 6), pp. 639–42, (2017).
5- Fletcher, J.W., P.E. Kinahan, "PET/CT standardized uptake values (SUVs) in clinical practice and assessing response to therapy." NIH Public Access, Vol. 31 (No. 6), pp. 496–505, (2010).
6- Lindholm, H., J. Staaf, H. Jacobsson, F. Brolin, R. Hatherly, A. Sânchez-Crespo, "Repeatability of the maximum standard uptake value (SUVmax) in FDG PET." Molecular imaging and radionuclide therapy, Vol. 23 (No. 1), pp. 16–20, (2014).
7- Beauregard, J.-M., A. Rahmim, "Harmonization of nomenclature for molecular imaging metrics of tumour burden: molecular tumour volume (MTV), total lesion activity (TLA) and total lesion fraction (TLF)." European journal of nuclear medicine and molecular imaging, Vol. 49 (No. 2), pp. 424–6, (2022).
8- Küper, A.T., D. Kersting, T. Telli, K. Herrmann, A. Rominger, A. Afshar-Oromieh, L. Lopes, S. Karkampouna, K. Shi, M. Kim, B. Hadaschik, C. Darr, L. Umutlu, W.P. Fendler, R. Seifert, "PSMA-PET follow-up to assess response in patients not receiving PSMA therapy: Is there value beyond localization of disease?" Theranostics, Vol. 14 (No. 9), pp. 3623–33, (2024).
9- Seifert, R., S. Rasul, K.E. Seifert, M. Eveslage, L. Rahbar Nikoukar, K. Kessel, M. Schäfers, J. Yu, A.R. Haug, M. Hacker, M. Bögemann, L. Bodei, M.J. Morris, M.S. Hofman, K. Rahbar, "A prognostic risk score for prostate cancer based on PSMA PET-derived organ-specific tumor volumes." Radiology, Vol. 307 (No. 4), pp. e222010, (2023).
10- Seifert, R., K. Kessel, K. Schlack, M. Weckesser, D. Kersting, K.E. Seitzer, M. Weber, M. Bögemann, K. Rahbar, "Total tumor volume reduction and low PSMA expression in patients receiving Lu-PSMA therapy." Theranostics, Vol. 11 (No. 17), pp. 8143–51, (2021).
11- Barbato, F., W.P. Fendler, I. Rauscher, K. Herrmann, A. Wetter, J. Ferdinandus, R. Seifert, M. Nader, K. Rahbar, B. Hadaschik, M. Eiber, A. Gafita, M. Weber, "PSMA-PET for the assessment of metastatic hormone-sensitive prostate cancer volume of disease." Journal of nuclear medicine: official publication, Society of Nuclear Medicine, Vol. 62 (No. 12), pp. 1747–50, (2021).
12- Seifert, R., K. Seitzer, K. Herrmann, K. Kessel, M. Schäfers, J. Kleesiek, M. Weckesser, M. Boegemann, K. Rahbar, "Analysis of PSMA expression and outcome in patients with advanced Prostate Cancer receiving 177Lu-PSMA-617 Radioligand Therapy." Theranostics, Vol. 10 (No. 17), pp. 7812–20, (2020).
13- Zeman, M.N., E.A. Akin, R.W. Merryman, H.A. Jacene, "Interim FDG-PET/CT for response assessment of lymphoma." Seminars in nuclear medicine, Vol. 53 (No. 3), pp. 371–88, (2023).
14- Cheson, B.D., R.I. Fisher, S.F. Barrington, F. Cavalli, L.H. Schwartz, E. Zucca, T.A. Lister, Alliance, Australasian Leukaemia and Lymphoma Group, Eastern Cooperative Oncology Group, European Mantle Cell Lymphoma Consortium, Italian Lymphoma Foundation, European Organisation for Research, Treatment of Cancer/Dutch Hemato-Oncology Group, Grupo Español de Médula Ósea, German High-Grade Lymphoma Study Group, German Hodgkin’s Study Group, Japanese Lymphorra Study Group, Lymphoma Study Association, NCIC Clinical Trials Group, Nordic Lymphoma Study Group, Southwest Oncology Group, United Kingdom National Cancer Research Institute, "Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification." Journal of clinical oncology: official journal of the American Society of Clinical Oncology, Vol. 32 (No. 27), pp. 3059–68, (2014).
15- Barrington, S.F., A.-S. Cottereau, J.M. Zijlstra, "Is 18F-FDG metabolic tumor volume in lymphoma really happening?" Journal of nuclear medicine: official publication, Society of Nuclear Medicine, Vol. 65 (No. 4), pp. 510–1, (2024).
16- Tricarico, P., D. Chardin, N. Martin, S. Contu, F. Hugonnet, J. Otto, O. Humbert, "Total metabolic tumor volume on 18F-FDG PET/CT is a game-changer for patients with metastatic lung cancer treated with immunotherapy." Journal for immunotherapy of cancer, Vol. 12 (No. 4), pp. e007628, (2024).
17- Annovazzi, A., V. Ferraresi, S. Rea, M. Russillo, D. Renna, S. Carpano, R. Sciuto, "Correction to: Prognostic value of total metabolic tumour volume and therapy-response assessment by [18F]FDG PET/CT in patients with metastatic melanoma treated with BRAF/MEK inhibitors." European radiology, Vol. 32 (No. 8), pp. 5783, (2022).
18- Zhou, M., Y. Chen, H. Huang, X. Zhou, J. Liu, G. Huang, "Prognostic value of total lesion glycolysis of baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography in diffuse large B-cell lymphoma." Oncotarget, Vol. 7 (No. 50), pp. 83544–53, (2016).
19- Kashyap, R., J.P. Buteau, M. Bressel, M. Eifer, N. Bollampally, P. Jackson, L. McIntosh, S. Sandhu, M.S. Hofman, "Prognostic value of posttherapy SPECT/CT for overall survival in patients undergoing [177Lu]Lu-PSMA-617 radiopharmaceutical therapy: Results from 3 clinical trials." Journal of nuclear medicine: official publication, Society of Nuclear Medicine, Vol. 66 (No. 8), pp. 1265–70, (2025).
20- John, N., S. Pathmanandavel, M. Crumbaker, W. Counter, B. Ho, A.O. Yam, P. Wilson, R. Niman, M. Ayers, A. Poole, A. Hickey, S. Agrawal, G. Perkins, A. Kallinen, E. Eslick, M.R. Stockler, A.M. Joshua, A. Nguyen, L. Emmett, "177Lu-PSMA SPECT quantitation at 6 weeks (dose 2) predicts short progression-free survival for patients undergoing 177Lu-PSMA-I&T therapy." Journal of nuclear medicine: official publication, Society of Nuclear Medicine, Vol. 64 (No. 3), pp. 410–5, (2023).
21- Song, H., M.I. Leonio, V. Ferri, H. Duan, C.M. Aparici, G. Davidzon, B.L. Franc, F. Moradi, J. Shah, C.P. Bergstrom, A.C. Fan, S. Shah, A.R. Khaki, S. Srinivas, A. Iagaru, "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." European journal of nuclear medicine and molecular imaging, Vol. 51 (No. 9), pp. 2784–93, (2024).
22- Uribe, C., A. Iravani, B. Savir-Baruch, H. Jacene, S.A. Graves, Y.K. Dewaraja, C.L. Heath, T.A. Hope, "Summary: SNMMI/ACNM procedure standard for posttreatment imaging of 177Lu-based radiopharmaceuticals." Journal of nuclear medicine: official publication, Society of Nuclear Medicine , (2025). doi:10.2967/jnumed.125.270979.
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| Files | ||
| Issue | Vol 13 No 2 (2026) | |
| Section | Systematic Review(s) | |
| DOI | https://doi.org/10.18502/fbt.v13i2.21952 | |
| Keywords | ||
| Prostate Specific Membrane Antigen Positron Emission Tomography/Computed Tomography Single Photon Emission Computerized Tomography/Computed Tomography Disease Burden Quantification Lesion Tracking Radiopharmaceutical Therapy Prostate Cancer Artificial Intelligent Segmentation Theranostics | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Yousefirizi F, Beauregard J-M, Rahmim A. Towards Routine AI-Based PET/CT and SPECT/CT Lesion Segmentation and Tracking in PSMA Theranostics. Frontiers Biomed Technol. 2026;13(2):592-600.
