{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T09:57:16Z","timestamp":1773827836218,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological developments and Innovations of Republic of Serbia","award":["451-03-137\/2025-03\/200110"],"award-info":[{"award-number":["451-03-137\/2025-03\/200110"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Objective: To evaluate Tc-99m-PSMA SPECT\/CT detection of biochemical recurrence (BCR) of prostate cancer across serum PSA levels in patients treated with radical prostatectomy or radiation therapy, to explore clinical\/pathologic predictors of scan positivity and metastatic disease, and to assess its potential role as a pragmatic alternative when PSMA PET\/CT is unavailable in resource-limited settings. Materials and Methods: In this prospective single-center study, we included 132 men with biochemical recurrence who underwent Tc-99m-PSMA SPECT\/CT between January 2024 and December 2025 after predefined inclusion and exclusion criteria were applied, and they were further stratified by primary treatment (radical prostatectomy or radiation therapy). Patients were followed up for up to 6 months after imaging to verify observed findings (histopathology, confirmatory imaging and PSA response) and a logistic regression was applied to identify predictors of scan positivity and metastatic disease. Results: In men initially treated with radical prostatectomy, detection increased from 38.9% at PSA 0.2 to &lt;2 ng\/mL to 63.2% at 2 to &lt;4 ng\/mL, 71.4% at 4 to &lt;7 ng\/mL, and 90% at PSA \u2265 7 ng\/mL (overall 69.1%). In the radiation therapy cohort, detection was 58.3% at PSA 2 to &lt;4 ng\/mL, rising to 85.7% at 4 to &lt;7 ng\/mL and 96% at PSA \u2265 7 ng\/mL (overall 84.3%). In the multivariable analysis, PSA doubling (log2[PSA]) independently predicted scan positivity and metastatic disease in both cohorts, while seminal vesicle invasion independently predicted metastatic spread in the post-prostatectomy group. Conclusions: Tc-99m-PSMA SPECT\/CT is a useful tool for detecting prostate cancer BCR, with performance strongly dependent on PSA and higher detection in patients with higher PSA levels. Increasing PSA independently predicted scan positivity and metastatic disease, while seminal vesicle invasion was independently associated with metastatic spread. In settings where PSMA PET\/CT is unavailable, Tc-99m-PSMA SPECT\/CT may represent a practical alternative, particularly for patients with elevated PSA.<\/jats:p>","DOI":"10.3390\/diagnostics16060895","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:35:08Z","timestamp":1773819308000},"page":"895","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Can Tc-99m-PSMA SPECT\/CT Be Used as Accessible Alternative for Diagnosis of Biochemically Recurrent Prostate Cancer? A Prospective Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8463-5932","authenticated-orcid":false,"given":"Veljkovi\u0107","family":"Milo\u0161","sequence":"first","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatovi\u0107","family":"Slobodanka","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pej\u010di\u0107","family":"Tomislav","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-4504","authenticated-orcid":false,"given":"Bukumiri\u0107","family":"Zoran","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"},{"name":"Institute of Medical Statistics and Informatics, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Odalovi\u0107","family":"Strahinja","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3301-9456","authenticated-orcid":false,"given":"Grozdi\u0107 Milojevi\u0107","family":"Isidora","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7170-4433","authenticated-orcid":false,"given":"Stojiljkovi\u0107","family":"Milica","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7168-8848","authenticated-orcid":false,"given":"Petrovi\u0107","family":"Jelena","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3993-7114","authenticated-orcid":false,"given":"Ivanovski","family":"Ana","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9600-090X","authenticated-orcid":false,"given":"\u0160obi\u0107","family":"\u0160aranovi\u0107 Dragana","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6078-4500","authenticated-orcid":false,"given":"Artiko","family":"Vera","sequence":"additional","affiliation":[{"name":"Center for Nuclear Medicine with PET, University Clinical Center of Serbia, 11000 Belgrade, Serbia"},{"name":"Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1002\/ijc.35278","article-title":"The GLOBOCAN 2022 cancer estimates: Data sources, methods, and a snapshot of the cancer burden worldwide","volume":"156","author":"Laversanne","year":"2025","journal-title":"Int. J. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Wang, L., Lu, B., He, M., Wang, Y., Wang, Z., and Du, L. (2022). Prostate cancer incidence and mortality: Global status and temporal trends in 89 countries from 2000 to 2019. Front. Public Health, 10.","DOI":"10.3389\/fpubh.2022.811044"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.eururo.2024.11.013","article-title":"Recent patterns and trends in global prostate cancer incidence and mortality: An update","volume":"87","author":"Schafer","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.eururo.2024.03.027","article-title":"EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on prostate cancer\u20142024 update. Part I: Screening, diagnosis, and local treatment with curative intent","volume":"86","author":"Cornford","year":"2024","journal-title":"Eur. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"140","DOI":"10.6004\/jnccn.2024.0019","article-title":"Prostate cancer, version 3.2024: Featured updates to the NCCN guidelines","volume":"22","author":"Schaeffer","year":"2024","journal-title":"JNCCN J. Natl. Compr. Canc. Netw."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1080\/21681805.2022.2108140","article-title":"Biochemical recurrence after radical prostatectomy\u2014A large, comprehensive, population-based study with long follow-up","volume":"56","author":"Stranne","year":"2022","journal-title":"Scand. J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.euf.2019.06.004","article-title":"Biochemical recurrence in prostate cancer: The European Association of Urology prostate cancer guidelines panel recommendations","volume":"6","author":"Bergh","year":"2020","journal-title":"Eur. Urol. Focus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e35612","DOI":"10.1002\/cncr.35612","article-title":"Implementing evidence-based strategies for men with biochemically recurrent and advanced prostate cancer: Consensus recommendations from the US prostate cancer conference 2024","volume":"131","author":"Bryce","year":"2025","journal-title":"Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.prnil.2022.05.001","article-title":"Diagnostic yield of multiparametric MRI for local recurrence at biochemical recurrence after radical prostatectomy","volume":"10","author":"Kim","year":"2022","journal-title":"Prostate Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S0090-4295(02)02411-1","article-title":"Limited value of bone scintigraphy and computed tomography in assessing biochemical failure after radical prostatectomy","volume":"61","author":"Kane","year":"2003","journal-title":"Urology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2967\/jnumed.121.263262","article-title":"Appropriate use criteria for prostate-specific membrane antigen PET imaging","volume":"63","author":"Jadvar","year":"2022","journal-title":"J. Nucl. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.urolonc.2013.09.003","article-title":"The prostate-specific membrane antigen: Lessons and current clinical implications from 20 years of research","volume":"32","author":"Ristau","year":"2014","journal-title":"Urol. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1158\/0008-5472.727.65.3","article-title":"Novel role of prostate-specific membrane antigen in suppressing prostate cancer invasiveness","volume":"65","author":"Ghosh","year":"2005","journal-title":"Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Hoffmann, M.A., von Eyben, F.E., Fischer, N., Rosar, F., M\u00fcller-H\u00fcbenthal, J., Buchholz, H.-G., Wieler, H.J., and Schreckenberger, M. (2022). Comparison of [18F]PSMA-1007 with [68Ga]Ga-PSMA-11 PET\/CT in restaging of prostate cancer patients with PSA relapse. Cancers, 14.","DOI":"10.3390\/cancers14061479"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium-177\u2013PSMA-617 for metastatic castration-resistant prostate cancer","volume":"385","author":"Sartor","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ma, J., Li, L., Liao, T., Gong, W., and Zhang, C. (2022). Efficacy and safety of 225Ac-PSMA-617-targeted alpha therapy in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.796657"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1007\/s00259-022-06089-w","article-title":"PSMA PET\/CT: Joint EANM procedure guideline\/SNMMI procedure standard for prostate cancer imaging 2.0","volume":"50","author":"Fendler","year":"2023","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Cuocolo, A., and Petretta, M. (2021). PET and SPECT Specialty Grand Challenge. When Knowledge Travels at the Speed of Light, Photons Take to the Field. Front. Nucl. Med., 1.","DOI":"10.3389\/fnume.2021.671914"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Wang, Q., Ketteler, S., and Bagheri, S. (2024). Diagnostic efficacy of [99mTc]Tc-PSMA SPECT\/CT for prostate cancer: A meta-analysis. BMC Cancer, 24.","DOI":"10.1186\/s12885-024-12734-4"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"422","DOI":"10.2967\/jnumed.120.247197","article-title":"Global Issues of Radiopharmaceutical Access and Availability: A Nuclear Medicine Global Initiative Project","volume":"62","author":"Cutler","year":"2021","journal-title":"J. Nucl. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s41824-024-00226-4","article-title":"Real world experience with [99mTc]Tc-HYNIC-iPSMA SPECT prostate cancer detection: Interim results from the global NOBLE registry","volume":"8","author":"Tually","year":"2024","journal-title":"EJNMMI Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","volume":"105","author":"Stevens","year":"2024","journal-title":"Kidney Int."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Li, B., Duan, L., Shi, J., Han, Y., Wei, W., Cheng, X., Cao, Y., Kader, A., Ding, D., and Wu, X. (2022). Diagnostic performance of 99mTc-HYNIC-PSMA SPECT\/CT for biochemically recurrent prostate cancer after radical prostatectomy. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1072437"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/pros.23444","article-title":"99mTc-MIP-1404-SPECT\/CT for the detection of PSMA-positive lesions in 225 patients with biochemical recurrence of prostate cancer","volume":"78","author":"Schmidkonz","year":"2018","journal-title":"Prostate"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.4103\/1008-682X.192638","article-title":"Evaluation of 99mTc-labeled PSMA-SPECT\/CT imaging in prostate cancer patients who have undergone biochemical relapse","volume":"19","author":"Su","year":"2017","journal-title":"Asian J. Androl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"17588359231221342","DOI":"10.1177\/17588359231221342","article-title":"Diagnostic value of [99mTc]Tc-PSMA-I&S-SPECT\/CT for the primary staging and restaging of prostate cancer","volume":"16","author":"Farkas","year":"2024","journal-title":"Ther. Adv. Med. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1007\/s00259-022-05970-y","article-title":"Flare on [18F]PSMA-1007 PET\/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: Possible marker of tumor aggressiveness in treatment-na\u00efve metastatic prostate cancer patients","volume":"50","author":"Malaspina","year":"2023","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1007\/s00259-018-4079-z","article-title":"Impact of long-term androgen deprivation therapy on PSMA ligand PET\/CT in patients with castration-sensitive prostate cancer","volume":"45","author":"Debus","year":"2018","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_29","first-page":"45","article-title":"[99mTc]Tc-PSMA-I&S-SPECT\/CT: Experience in prostate cancer imaging in an outpatient centre","volume":"10","author":"Werner","year":"2020","journal-title":"Eur. J. Nucl. Med. Mol. Imaging Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.euros.2023.12.001","article-title":"The Probability of Metastases Within Different Prostate-specific Antigen Ranges Using Prostate-specific Membrane Antigen Positron Emission Tomography in Patients with Newly Diagnosed Prostate Cancer","volume":"59","author":"Luining","year":"2024","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_31","first-page":"190","article-title":"Seminal Vesicle Invasion by Prostate Cancer: Prognostic Significance and Therapeutic Implications","volume":"2","author":"Potter","year":"2000","journal-title":"Rev. Urol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1002\/cncr.21895","article-title":"Cancer-specific survival and predictors of prostate-specific antigen recurrence and survival in patients with seminal vesicle invasion after radical prostatectomy","volume":"106","author":"Secin","year":"2006","journal-title":"Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.eururo.2025.05.006","article-title":"The role of prostate-specific membrane antigen positron emission tomography for assessment of local recurrence and distant metastases in patients with biochemical recurrence of prostate cancer after definitive treatment: A systematic review and meta-analysis","volume":"88","author":"Mazzone","year":"2025","journal-title":"Eur. Urol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1007\/s00259-021-05189-3","article-title":"Performance of [68Ga]Ga-PSMA-11 PET\/CT in patients with recurrent prostate cancer after prostatectomy\u2014A multi-centre evaluation of 2533 patients","volume":"48","author":"Wagner","year":"2021","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_35","first-page":"1","article-title":"Direct comparison of [99mTc]Tc-PSMA SPECT\/CT and [68Ga]Ga-PSMA PET\/CT in patients with prostate cancer","volume":"8","author":"Albalooshi","year":"2020","journal-title":"Asia-Ocean. J. Nucl. Med. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1002\/pros.23379","article-title":"Diagnostic sensitivity of Tc-99m HYNIC-PSMA SPECT\/CT in prostate carcinoma: A comparative analysis with 18F-Ga-PSMA PET\/CT","volume":"77","author":"Lawal","year":"2017","journal-title":"Prostate"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/MNM.0000000000001361","article-title":"Comparison of the diagnostic utility of [99mTc]Tc-PSMA scintigraphy versus [68Ga]Ga-PSMA-11 PET\/CT in the detection of metastatic prostate cancer and dosimetry analysis: A gamma-camera-based alternate PSMA imaging modality","volume":"42","author":"Singh","year":"2021","journal-title":"Nucl. Med. Commun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s40658-022-00434-6","article-title":"What Validation Tests Can Be Done by the Clinical Medical Physicist While Waiting for the Standardization of Quantitative SPECT\/CT Imaging?","volume":"9","author":"Birkenfeld","year":"2022","journal-title":"EJNMMI Phys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1007\/s00259-022-06028-9","article-title":"EANM Practice Guideline for Quantitative SPECT-CT","volume":"50","author":"Dickson","year":"2023","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1186\/s43055-021-00562-6","article-title":"Comparison of 99mTc-PSMA SPECT\/CT and 68Ga-PSMA PET\/CT in patients with prostate cancer: A protocol for systematic review and meta-analysis","volume":"52","author":"Yunusa","year":"2021","journal-title":"Egypt J. Radiol. Nucl. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Brunello, S., Salvarese, N., Carpanese, D., Gobbi, C., Melendez-Alafort, L., and Bolzati, C. (2022). A review on the current state and future perspectives of [99mTc]Tc-Housed PSMA-i in prostate cancer. Molecules, 27.","DOI":"10.3390\/molecules27092617"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/6\/895\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T07:47:09Z","timestamp":1773820029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/16\/6\/895"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":41,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["diagnostics16060895"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics16060895","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,18]]}}}