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Fibroblast activation protein alpha (FAP) identifies activated myofibroblasts post-MI, however its spatial distribution relative to the scar and area at risk (AAR) is unclear. Non-invasive FAP-imaging with PET radiotracer\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga-FAPI-46 shows uptake beyond the infarct scar. We therefore aimed to characterize FAP expression in the AAR using a myocardial ischemia\u2013reperfusion (MI\/R) model in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      We induced MI\/R in male C57BL\/6N mice. The AAR was identified by\n                      <jats:italic>in vivo<\/jats:italic>\n                      lectin staining, and expression of FAP, CD68, and hypoxic tissues were measured using immunohistochemistry. Spatial FAP was further interrogated by\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga-FAPI-46 in mice by autoradiography and humans by PET. Additionally, human cardiac tissues from acute MI patients were examined for fibroblasts and inflammatory cells by expression of FAP, CD13, and \u03b1-smooth muscle actin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      FAP expression peaked three days post-MI\/R predominantly within the AAR (p\u2009&lt;\u20090.05 vs. d0). Consistent between murine models and human tissues, FAP\n                      <jats:sup>+<\/jats:sup>\n                      myofibroblasts accumulated within the infarct scar and borderzone, occasionally extending into non-ischemic myocardium. CD68\n                      <jats:sup>+<\/jats:sup>\n                      macrophages peaked similarly at three days post-MI\/R (p\u2009&lt;\u20090.05 vs. d0). FAP expression weakly correlated with CD68 but not with extent of ischemic or hypoxic territory post-MI\/R. FAP imaging in mice and humans revealed aligned non-uniform\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga-FAPI-46 uptake extending from the infarct scar into surviving myocardium after MI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate a distinct FAP expression pattern post-MI\/R. The alignment of\n                      <jats:italic>ex vivo<\/jats:italic>\n                      <jats:sup>68<\/jats:sup>\n                      \u00a0Ga-FAPI-46 signal with myofibroblasts in the AAR supports its identification of a unique substrate in myocardial injury complementing other non-invasive imaging measurements of perfusion, viability and fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-025-01994-6","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T10:28:59Z","timestamp":1740997739000},"page":"173-183","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Spatial FAP Expression as Detected by 68\u00a0Ga-FAPI-46 Identifies Myofibroblasts Beyond the Infarct Scar After Reperfusion"],"prefix":"10.1007","volume":"27","author":[{"given":"Annika","family":"Hess","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Renko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Sch\u00e4fer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Fraccarollo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan D.","family":"Schmitto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Diekmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Thum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank M.","family":"Bengel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Bauersachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James T.","family":"Thackeray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-5484","authenticated-orcid":false,"given":"Jochen","family":"Tillmanns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,3]]},"reference":[{"key":"1994_CR1","doi-asserted-by":"publisher","first-page":"e618","DOI":"10.1161\/CIR.0000000000000617","volume":"138","author":"K Thygesen","year":"2018","unstructured":"Thygesen K, Alpert JS, Jaffe AS et al (2018) Fourth universal definition of myocardial infarction (2018). 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