{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T21:48:28Z","timestamp":1793915308436,"version":"4.8.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":83,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Imaging"],"DOI":"10.1186\/s40644-026-01084-y","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T15:43:11Z","timestamp":1783006991000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["When PSMA is not enough: the diagnostic blind spots of PSMA PET\/CT and the added value of [\u00b9\u2078F]FDG in high-risk prostate cancer: dual-tracer cohort study"],"prefix":"10.1186","volume":"26","author":[{"given":"Efrah Ahmed","family":"Ibrahim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eray","family":"Alper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"issue":"5","key":"1084_CR1","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1007\/s00259-022-06089-w","volume":"50","author":"WP Fendler","year":"2023","unstructured":"Fendler WP, Eiber M, Beheshti M, et al. PSMA PET\/CT: joint EANM procedure guideline\/SNMMI procedure standard for prostate cancer imaging 2.0. Eur J Nucl Med Mol Imaging. 2023;50(5):1466\u201386. https:\/\/doi.org\/10.1007\/s00259-022-06089-w.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"11","key":"1084_CR2","doi-asserted-by":"publisher","first-page":"1635","DOI":"10.1001\/jamaoncol.2021.3771","volume":"7","author":"TA Hope","year":"2021","unstructured":"Hope TA, Eiber M, Armstrong WR, et al. Diagnostic Accuracy of \u2076\u2078Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial. JAMA Oncol. 2021;7(11):1635\u201342. https:\/\/doi.org\/10.1001\/jamaoncol.2021.3771.","journal-title":"JAMA Oncol"},{"issue":"2","key":"1084_CR3","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.eururo.2025.05.006","volume":"88","author":"E Mazzone","year":"2025","unstructured":"Mazzone E, Thomson A, Chen DC, et al. 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. Eur Urol. 2025;88(2):129\u201341. https:\/\/doi.org\/10.1016\/j.eururo.2025.05.006.","journal-title":"Eur Urol"},{"issue":"1","key":"1084_CR4","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41391-024-00850-y","volume":"28","author":"A Mari","year":"2025","unstructured":"Mari A, Cadenar A, Giudici S, et al. A systematic review and meta-analysis to evaluate the diagnostic accuracy of PSMA PET\/CT in the initial staging of prostate cancer. Prostate Cancer Prostatic Dis. 2025;28(1):56\u201369. https:\/\/doi.org\/10.1038\/s41391-024-00850-y.","journal-title":"Prostate Cancer Prostatic Dis"},{"issue":"5","key":"1084_CR5","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1007\/s00432-025-06184-z","volume":"151","author":"Z Shen","year":"2025","unstructured":"Shen Z, Li Z, Li Y, et al. PSMA PET\/CT for prostate cancer diagnosis: current applications and future directions. J Cancer Res Clin Oncol. 2025;151(5):155. https:\/\/doi.org\/10.1007\/s00432-025-06184-z. Published 2025 May 4.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"1","key":"1084_CR6","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41585-024-00900-z","volume":"22","author":"MK Bakht","year":"2025","unstructured":"Bakht MK, Beltran H. Biological determinants of PSMA expression, regulation, and heterogeneity in prostate cancer. Nat Rev Urol. 2025;22(1):26\u201345. https:\/\/doi.org\/10.1038\/s41585-024-00900-z.","journal-title":"Nat Rev Urol"},{"issue":"1","key":"1084_CR7","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1038\/s41420-024-02031-1","volume":"10","author":"D Zheng","year":"2024","unstructured":"Zheng D, Zhang Y, Yang S, et al., et al. Androgen deprivation induces neuroendocrine phenotypes in prostate cancer cells through CREB1\/EZH2-mediated downregulation of REST. Cell Death Discov. 2024;10(1):246. https:\/\/doi.org\/10.1038\/s41420-024-02031-1. Published 2024 May 22.","journal-title":"Cell Death Discov"},{"issue":"1","key":"1084_CR8","doi-asserted-by":"publisher","first-page":"2548975","DOI":"10.1080\/07853890.2025.2548975","volume":"57","author":"B Shao","year":"2025","unstructured":"Shao B, Zeng Y. Mechanisms of neuroendocrine differentiation in castration-resistant prostate cancer and advances in the treatment of neuroendocrine prostate cancer. Ann Med. 2025;57(1):2548975. https:\/\/doi.org\/10.1080\/07853890.2025.2548975.","journal-title":"Ann Med"},{"issue":"2\u20133","key":"1084_CR9","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s10555-013-9474-0","volume":"33","author":"Z Culig","year":"2014","unstructured":"Culig Z, Santer FR. Androgen receptor signaling in prostate cancer. Cancer Metastasis Rev. 2014;33(2\u20133):413\u201327. https:\/\/doi.org\/10.1007\/s10555-013-9474-0.","journal-title":"Cancer Metastasis Rev"},{"issue":"1","key":"1084_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/CU9.0000000000000312","volume":"20","author":"Y Shao","year":"2026","unstructured":"Shao Y, Liu Z, Ma J, et al. Molecular mechanisms and classification of castration-resistant prostate cancer: Insights into androgen receptor, cancer stem cells, and neuroendocrine features. Curr Urol. 2026;20(1):1\u201314. https:\/\/doi.org\/10.1097\/CU9.0000000000000312.","journal-title":"Curr Urol"},{"issue":"3","key":"1084_CR11","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1007\/s13139-024-00839-4","volume":"58","author":"A Mahalik","year":"2024","unstructured":"Mahalik A, Jaleel J, Sagar S, Khan D, Raju S, Kumar R. Discordant Molecular Imaging Findings with 2-[\u00b9\u2078F]FDG and [\u2076\u2078Ga]Ga-PSMA PET\/CT in a Patient with Both Bladder and Prostate Cancer. Nucl Med Mol Imaging. 2024;58(3):150\u20131. https:\/\/doi.org\/10.1007\/s13139-024-00839-4.","journal-title":"Nucl Med Mol Imaging"},{"issue":"23","key":"1084_CR12","doi-asserted-by":"publisher","first-page":"9663","DOI":"10.1158\/0008-5472.CAN-08-2229","volume":"68","author":"X Deng","year":"2008","unstructured":"Deng X, Liu H, Huang J, et al. Ionizing radiation induces prostate cancer neuroendocrine differentiation through interplay of CREB and ATF2: implications for disease progression. Cancer Res. 2008;68(23):9663\u201370. https:\/\/doi.org\/10.1158\/0008-5472.CAN-08-2229.","journal-title":"Cancer Res"},{"issue":"4","key":"1084_CR13","doi-asserted-by":"publisher","first-page":"541","DOI":"10.4103\/1008-682X.123669","volume":"16","author":"J Lipianskaya","year":"2014","unstructured":"Lipianskaya J, Cohen A, Chen CJ, et al. Androgen-deprivation therapy-induced aggressive prostate cancer with neuroendocrine differentiation. Asian J Androl. 2014;16(4):541\u20134. https:\/\/doi.org\/10.4103\/1008-682X.123669.","journal-title":"Asian J Androl"},{"key":"1084_CR14","doi-asserted-by":"publisher","unstructured":"Van Hemelrijck M, Feller A, Garmo H, et al. Incidence of second malignancies for prostate cancer. PLoS One. 2014;9(7):e102596. Published 2014 Jul 21. https:\/\/doi.org\/10.1371\/journal.pone.0102596.","DOI":"10.1371\/journal.pone.0102596"},{"issue":"1","key":"1084_CR15","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1007\/s10238-025-01654-7","volume":"25","author":"J Taveira-Barbosa","year":"2025","unstructured":"Taveira-Barbosa J, Morais S, Garcia T, Bento MJ, Lunet N. Second primary cancers among males with a first primary prostate cancer: a population-based study in Northern Portugal. Clin Exp Med. 2025;25(1):122. https:\/\/doi.org\/10.1007\/s10238-025-01654-7.","journal-title":"Clin Exp Med"},{"key":"1084_CR16","doi-asserted-by":"publisher","first-page":"1607227","DOI":"10.3389\/fmed.2025.1607227","volume":"12","author":"CM Iacovitti","year":"2025","unstructured":"Iacovitti CM, Cuzzocrea M, Rizzo A, et al. Diagnostic value of dual-tracer PET\/CT with [\u00b9\u2078F]FDG and PSMA ligands in prostate cancer: an updated systematic review. Front Med (Lausanne). 2025;12:1607227. https:\/\/doi.org\/10.3389\/fmed.2025.1607227. Published 2025 Jul 9.","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"1084_CR17","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2967\/jnumed.120.262250","volume":"63","author":"R Chen","year":"2022","unstructured":"Chen R, Wang Y, Zhu Y, et al. The Added Value of [\u00b9\u2078F]-FDG PET\/CT Compared with \u2076\u2078Ga-PSMA PET\/CT in Patients with Castration-Resistant Prostate Cancer. J Nucl Med. 2022;63(1):69\u201375. https:\/\/doi.org\/10.2967\/jnumed.120.262250.","journal-title":"J Nucl Med"},{"key":"1084_CR18","doi-asserted-by":"publisher","first-page":"175883592312205","DOI":"10.1177\/17588359231220506","volume":"16","author":"J Pan","year":"2024","unstructured":"Pan J, Zhang T, Chen S, et al. Nomogram to predict the presence of PSMA-negative but FDG-positive lesion in castration-resistant prostate cancer: a multicenter cohort study. Ther Adv Med Oncol. 2024;16:17588359231220506. https:\/\/doi.org\/10.1177\/17588359231220506. Published 2024 Jan 6.","journal-title":"Ther Adv Med Oncol"},{"issue":"9","key":"1084_CR19","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.1007\/s00259-025-07198-y","volume":"52","author":"T Telli","year":"2025","unstructured":"Telli T, Lopes L, Karpinski M, et al. Prognostic value of [\u00b9\u2078F]FDG- and PSMA-PET in patients evaluated for [\u00b9\u2077\u2077Lu]Lu-PSMA therapy of mCRPC. Eur J Nucl Med Mol Imaging. 2025;52(9):3199\u2013210. https:\/\/doi.org\/10.1007\/s00259-025-07198-y.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"1084_CR20","doi-asserted-by":"publisher","first-page":"1544208","DOI":"10.1155\/2021\/1544208","volume":"2021","author":"S McGeorge","year":"2021","unstructured":"McGeorge S, Kwok M, Jiang A, et al. Dual-Tracer Positron-Emission Tomography Using Prostate-Specific Membrane Antigen and Fluorodeoxyglucose for Staging of Prostate Cancer: A Systematic Review. Adv Urol. 2021;2021:1544208. https:\/\/doi.org\/10.1155\/2021\/1544208. Published 2021 Aug 18.","journal-title":"Adv Urol"},{"issue":"4","key":"1084_CR21","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.jclinepi.2007.11.008","volume":"61","author":"E von Elm","year":"2008","unstructured":"von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008;61(4):344\u20139. https:\/\/doi.org\/10.1016\/j.jclinepi.2007.11.008.","journal-title":"J Clin Epidemiol"},{"key":"1084_CR22","doi-asserted-by":"publisher","unstructured":"Hird AE, Magee DE, Matta R, et al. Assessment of secondary sarcomas among patients with cancer of the abdomen or pelvis who received combinations of surgery, radiation, and chemotherapy vs surgery alone. JAMA Netw Open. 2020;3(10):e2013929. Published 2020 Oct 1. https:\/\/doi.org\/10.1001\/jamanetworkopen.2020.13929.","DOI":"10.1001\/jamanetworkopen.2020.13929"},{"issue":"1","key":"1084_CR23","doi-asserted-by":"publisher","first-page":"102274","DOI":"10.1016\/j.clgc.2024.102274","volume":"23","author":"R Gagnon","year":"2025","unstructured":"Gagnon R, Kish EK, Cook S, et al. Real-world Clinical Outcomes and Prognostic Factors in Neuroendocrine Prostate Cancer. Clin Genitourin Cancer. 2025;23(1):102274. https:\/\/doi.org\/10.1016\/j.clgc.2024.102274.","journal-title":"Clin Genitourin Cancer"},{"issue":"13","key":"1084_CR24","doi-asserted-by":"publisher","first-page":"2143","DOI":"10.12998\/wjcc.v12.i13.2143","volume":"12","author":"M Wishahi","year":"2024","unstructured":"Wishahi M. Treatment-induced neuroendocrine prostate cancer and de novo neuroendocrine prostate cancer: Identification, prognosis and survival, genetic and epigenetic factors. World J Clin Cases. 2024;12(13):2143\u20136. https:\/\/doi.org\/10.12998\/wjcc.v12.i13.2143.","journal-title":"World J Clin Cases"},{"issue":"2","key":"1084_CR25","doi-asserted-by":"publisher","first-page":"13746","DOI":"10.4081\/aiua.2025.13746","volume":"97","author":"P Pepe","year":"2025","unstructured":"Pepe P, Pepe L, Cignoli D, Roscigno M. PSMA PET\/CT in the diagnosis of prostate cancer: why and when? Arch Ital Urol Androl. 2025;97(2):13746. https:\/\/doi.org\/10.4081\/aiua.2025.13746.","journal-title":"Arch Ital Urol Androl"},{"issue":"1","key":"1084_CR26","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40644-016-0072-6","volume":"16","author":"I Rauscher","year":"2016","unstructured":"Rauscher I, Maurer T, Fendler WP, Sommer WH, Schwaiger M, Eiber M. \u2076\u2078Ga-PSMA ligand PET\/CT in patients with prostate cancer: How we review and report. Cancer Imaging. 2016;16(1):14. https:\/\/doi.org\/10.1186\/s40644-016-0072-6.","journal-title":"Cancer Imaging"},{"key":"1084_CR27","doi-asserted-by":"publisher","unstructured":"Sheikhbahaei S, et al. Pearls and pitfalls in clinical interpretation of prostate-specific membrane antigen (PSMA)-targeted PET imaging. Eur J Nucl Med Mol Imaging. 2017;44(12): 2117-36. https:\/\/doi.org\/10.1007\/s00259-017-3780-7.","DOI":"10.1007\/s00259-017-3780-7"},{"issue":"13","key":"1084_CR28","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1002\/cncr.28695","volume":"120","author":"GW Warren","year":"2014","unstructured":"Warren GW, Alberg AJ, Kraft AS, Cummings KM. The 2014 Surgeon General\u2019s report: The health consequences of smoking-50 years of progress: a paradigm shift in cancer care. Cancer. 2014;120(13):1914\u20136. https:\/\/doi.org\/10.1002\/cncr.28695.","journal-title":"Cancer"},{"issue":"12","key":"1084_CR29","doi-asserted-by":"publisher","first-page":"1899","DOI":"10.2967\/jnumed.124.268288","volume":"65","author":"K Michalski","year":"2024","unstructured":"Michalski K, Kosmala A, Hartrampf PE, et al. [\u00b9\u2078F]FDG and [\u2076\u2078Ga]Ga-FAPI-04 Imaging for Outcome Prediction in Patients with High-Grade Neuroendocrine Neoplasms. J Nucl Med. 2024;65(12):1899\u2013903. https:\/\/doi.org\/10.2967\/jnumed.124.268288. Published 2024 Dec 3.","journal-title":"J Nucl Med"},{"issue":"9","key":"1084_CR30","doi-asserted-by":"publisher","first-page":"2830","DOI":"10.1007\/s00259-023-06255-8","volume":"50","author":"C Kratochwil","year":"2023","unstructured":"Kratochwil C, Fendler WP, Eiber M, et al. Joint EANM\/SNMMI procedure guideline for the use of [\u00b9\u2077\u2077Lu]-labeled PSMA-targeted radioligand-therapy ([\u00b9\u2077\u2077Lu]-PSMA-RLT). Eur J Nucl Med Mol Imaging. 2023;50(9):2830\u201345. https:\/\/doi.org\/10.1007\/s00259-023-06255-8.","journal-title":"Eur J Nucl Med Mol Imaging"},{"issue":"10276","key":"1084_CR31","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1016\/S0140-6736(21)00237-3","volume":"397","author":"MS Hofman","year":"2021","unstructured":"Hofman MS, Emmett L, Sandhu S, et al. [\u00b9\u2077\u2077Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397(10276):797\u2013804. https:\/\/doi.org\/10.1016\/S0140-6736(21)00237-3.","journal-title":"Lancet"},{"issue":"12","key":"1084_CR32","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","volume":"385","author":"O Sartor","year":"2021","unstructured":"Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385(12):1091\u2013103. https:\/\/doi.org\/10.1056\/NEJMoa2107322.","journal-title":"N Engl J Med"},{"issue":"4","key":"1084_CR33","doi-asserted-by":"publisher","first-page":"339","DOI":"10.2967\/jnmt.123.265779","volume":"51","author":"A Chalikandy","year":"2023","unstructured":"Chalikandy A, Yadav S, Basu S. Differentiation of Discordant Lesions on Dual-Tracer PET\/CT (\u2076\u2078Ga-PSMA-11 and [\u00b9\u2078F]-FDG) in Prostate Carcinoma: Diagnosis of Second Primary Malignancies. J Nucl Med Technol. 2023;51(4):339\u201342. https:\/\/doi.org\/10.2967\/jnmt.123.265779. Published 2023 Dec 5.","journal-title":"J Nucl Med Technol"}],"container-title":["Cancer Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40644-026-01084-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40644-026-01084-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40644-026-01084-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:02:10Z","timestamp":1790161330000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40644-026-01084-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1084"],"URL":"https:\/\/doi.org\/10.1186\/s40644-026-01084-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-9598282\/v1","asserted-by":"object"}]},"ISSN":["1470-7330"],"issn-type":[{"value":"1470-7330","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"assertion":[{"value":"3 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This retrospective study was approved by the Institutional Review Board (Approval Number: 2026\/154\/6\u2009\u2212\u20092). All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The requirement for informed consent was waived due to the retrospective design.","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors affirm that human research participants provided informed consent for publication of the images in Figs.\u00a0\n                      \n                      ,\n                      \n                      ,\n                      \n                      ,\n                      \n                      ,\n                      \n                      ,\n                      \n                      ,\n                      \n                      , and\n                      \n                      . All patient images are anonymized to protect participant identity.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"136"}}