{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:19:41Z","timestamp":1790734781049,"version":"4.1.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:00:00Z","timestamp":1771200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005788","name":"Medical University of Vienna","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005788","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Nucl Med Mol Imaging"],"published-print":{"date-parts":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Aortic stenosis (AS) induces myocardial remodeling and fibroblast activation, yet modifiable biomarkers capable of capturing active fibrogenesis and predicting post-transcatheter aortic valve implantation (TAVI) recovery are currently scarce. Fibroblast activation protein (FAP)\u2013targeted PET serves as a noninvasive tool to visualize activated fibroblasts in vivo. We evaluated a time-robust, blood-pool\u2013normalized myocardial [\n 68<\/jats:sup>\n Ga]Ga-FAPI PET imaging biomarker that reflects AS burden and predicts outcomes after TAVI.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Nineteen patients with severe symptomatic AS underwent [\n 68<\/jats:sup>\n Ga]Ga-FAPI-04 PET\/CT at 60, 70, and 120\u00a0min. Using an in-house semi-automatic pipeline, the left ventricular (LV) myocardium was segmented, and regions of elevated fibroblast activity (EFM) were delineated using a blood-pool\u2013anchored, time-point\u2013specific threshold. We quantified myocardial SUV\n mean<\/jats:sub>\n , blood-pool SUV\n mean<\/jats:sub>\n , and a normalized myocardium-to-blood index, TBR(EFM), and assessed associations with N-terminal pro-brain natriuretic peptide (NT-proBNP) and left-ventricular ejection fraction (LVEF). One-year outcomes (\n n<\/jats:italic>\n \u2009=\u200911) were assessed using a predefined composite clinical response.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Blood-pool SUV\n mean<\/jats:sub>\n declined from 60 to 120\u00a0min, whereas myocardial SUV\n mean<\/jats:sub>\n decreased less, yielding stable TBR(EFM) across time points (60\/70\/120 min: 2.2\u2009\u00b1\u20090.8, 2.1\u2009\u00b1\u20090.9, 2.3\u2009\u00b1\u20090.9; ANOVA\n p<\/jats:italic>\n \u2009=\u20090.596). By contrast, myocardial SUV\n mean<\/jats:sub>\n fell from 3.8\u2009\u00b1\u20090.7 (60\u00a0min) to 2.1\u2009\u00b1\u20090.9 (120\u00a0min;\n p<\/jats:italic>\n \u2009<\u20090.001). TBR(EFM) correlated with NT-proBNP at all time-points (60\u00a0min\n r<\/jats:italic>\n \u2009=\u20090.65,\n p<\/jats:italic>\n \u2009=\u20090.007; 120\u00a0min\n r<\/jats:italic>\n \u2009=\u20090.72,\n p<\/jats:italic>\n \u2009=\u20090.003), whereas SUV\n mean<\/jats:sub>\n did not (60\u00a0min\n p<\/jats:italic>\n \u2009=\u20090.576; 120\u00a0min\n p<\/jats:italic>\n \u2009=\u20090.109). Baseline TBR(EFM) was significantly lower in one-year responders than non-responders (1.7\u2009\u00b1\u20090.2 vs. 2.9\u2009\u00b1\u20090.9;\n p<\/jats:italic>\n \u2009=\u20090.013), with separation present at each time point (\n p<\/jats:italic>\n \u2009<\u20090.05). Higher baseline TBR(EFM) associated with lower reductions in NT-proBNP at one year (\n p<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Myocardial [\n 68<\/jats:sup>\n Ga]Ga-FAPI TBR may provide a time-robust index of active fibroblast signaling that relates to myocardial hemodynamic stress and stratifies one-year clinical response after TAVI. A single 60-minute acquisition with TBR quantification may be sufficient for myocardial [\n 68<\/jats:sup>\n Ga]Ga-FAPI assessment. These hypothesis-generating findings require validation in larger, multicenter cohorts.\n <\/jats:p>\n <\/jats:sec>\n \n Graphical abstract<\/jats:title>\n <\/jats:sec>","DOI":"10.1007\/s00259-026-07815-4","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T00:52:45Z","timestamp":1771203165000},"page":"4078-4087","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Time-robust myocardial [68Ga]Ga-FAPI PET biomarker reflects aortic stenosis severity and predicts post-TAVI outcomes"],"prefix":"10.1007","volume":"53","author":[{"given":"Song","family":"Xue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianling","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksa","family":"Lazarevi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Hamzaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Binder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Nitsche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Kiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno K","family":"Podesser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Hacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0016-6233","authenticated-orcid":false,"given":"Xiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaella","family":"Calabretta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,16]]},"reference":[{"key":"7815_CR1","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.cpet.2023.03.004","volume":"18","author":"J Diekmann","year":"2023","unstructured":"Diekmann J, Bengel FM. Cardiac applications of fibroblast activation protein imaging. PET Clin. 2023;18:389\u201396. https:\/\/doi.org\/10.1016\/j.cpet.2023.03.004.","journal-title":"PET Clin"},{"key":"7815_CR2","first-page":"1748","volume":"8","author":"L Nombela-Franco","year":"2015","unstructured":"Nombela-Franco L, Trigo Md, Morrison-Polo G, Veiga G, Jimenez-Quevedo P, Abdul-Jawad Altisent O, et al. Incidence, causes, and predictors of early (\u2264\u200930 days) and late unplanned hospital readmissions after transcatheter aortic valve replacement. JACC: Cardiovasc Interventions. 2015;8:1748\u201357.","journal-title":"JACC: Cardiovasc Interventions"},{"key":"7815_CR3","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1093\/eurheartj\/ehx182","volume":"38","author":"A Franzone","year":"2017","unstructured":"Franzone A, Pilgrim T, Arnold N, Heg D, Langhammer B, Piccolo R, et al. Rates and predictors of hospital readmission after transcatheter aortic valve implantation. 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Eur J Nucl Med Mol Imaging. 2023;50:839\u201348.","journal-title":"Eur J Nucl Med Mol Imaging"},{"key":"7815_CR17","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1056\/NEJMoa2500366","volume":"392","author":"S Raposeiras-Roubin","year":"2025","unstructured":"Raposeiras-Roubin S, Amat-Santos IJ, Rossello X, Gonz\u00e1lez Ferreiro R, Gonz\u00e1lez Berm\u00fadez I, Lopez Otero D, et al. Dapagliflozin in patients undergoing transcatheter Aortic-Valve implantation. N Engl J Med. 2025;392:1396\u2013405. https:\/\/doi.org\/10.1056\/NEJMoa2500366.","journal-title":"N Engl J Med"},{"key":"7815_CR18","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.2967\/jnumed.119.226993","volume":"60","author":"Z Varasteh","year":"2019","unstructured":"Varasteh Z, Mohanta S, Robu S, Braeuer M, Li Y, Omidvari N, et al. Molecular imaging of fibroblast activity after myocardial infarction using a 68Ga-labeled fibroblast activation protein inhibitor, FAPI-04. J Nucl Med. 2019;60:1743\u20139.","journal-title":"J Nucl Med"}],"container-title":["European Journal of Nuclear Medicine and Molecular Imaging"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-07815-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00259-026-07815-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00259-026-07815-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T07:25:50Z","timestamp":1777274750000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00259-026-07815-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,16]]},"references-count":18,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["7815"],"URL":"https:\/\/doi.org\/10.1007\/s00259-026-07815-4","relation":{},"ISSN":["1619-7070","1619-7089"],"issn-type":[{"value":"1619-7070","type":"print"},{"value":"1619-7089","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,16]]},"assertion":[{"value":"24 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All patients with severe, symptomatic AS who were scheduled for TAVI and underwent [68Ga]Ga-FAPI-04 PET\/CT at the Division of Nuclear Medicine, Medical University of Vienna, as part of clinical studies (Approval Nr. 1971\/2023 and Approval Nr. 1400\/2000).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors have read this manuscript and would like to have it considered exclusively for publication.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}},{"value":"Marcus Hacker is an editor of EJNMMI.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}