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Though considered benign, endometriotic lesions possess tumor-like properties such as tissue invasion and remodeling of the extracellular matrix. One major clinical hurdle concerning endometriosis is its diagnosis. The diagnostic modalities ultrasound and MRI are often unable to detect all lesions, and a clear correlation between imaging and clinical symptoms is still controversial. Therefore, it was our aim to identify a potential target to image active endometriotic lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      For our studies, we employed the preclinical radiotracer [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-FnBPA5, which specifically binds to relaxed fibronectin\u2013an extracellular matrix protein with key functions in homeostasis that has been implicated in the pathogenesis of diseases such as cancer and fibrosis. We employed this tracer in biodistribution as well as SPECT\/CT studies in mice and conducted immunohistochemical stainings on mouse uterine tissue as well as on patient-derived endometriosis tissue. In biodistribution and SPECT\/CT studies using the radiotracer [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-FnBPA5, we found that radiotracer uptake in the myometrium varies with the estrous cycle of the mouse, leading to higher uptake of [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-FnBPA5 during estrogen-dependent phases, which indicates an increased abundance of relaxed fibronectin when estrogen levels are high. Finally, immunohistochemical analysis of patient samples demonstrated that there is preferential relaxation of fibronectin in the proximity of the endometriotic stroma.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Estrous cycle stages characterized by high estrogen levels result in a higher abundance of relaxed fibronectin in the murine myometrium. This finding together with a first proof-of-concept study employing human endometriosis tissues suggests that relaxed fibronectin could be a potential target for the development of a diagnostic radiotracer targeting endometriotic lesions. With [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-FnBPA5, the matching targeting molecule is in preclinical development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13550-024-01070-0","type":"journal-article","created":{"date-parts":[[2024,2,10]],"date-time":"2024-02-10T10:03:37Z","timestamp":1707559417000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Relaxed fibronectin: a potential novel target for imaging endometriotic lesions"],"prefix":"10.1186","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5177-4167","authenticated-orcid":false,"given":"Belinda","family":"Trachsel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Imobersteg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Valpreda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8090-7267","authenticated-orcid":false,"given":"Gad","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regula","family":"Grabherr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ormos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8029-8692","authenticated-orcid":false,"given":"Irene A.","family":"Burger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-8697","authenticated-orcid":false,"given":"Rahel A.","family":"Kubik-Huch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-3833","authenticated-orcid":false,"given":"Roger","family":"Schibli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2898-7671","authenticated-orcid":false,"given":"Viola","family":"Vogel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1110-2665","authenticated-orcid":false,"given":"Martin","family":"B\u00e9h\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,10]]},"reference":[{"issue":"2","key":"1070_CR1","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1016\/j.fertnstert.2011.05.087","volume":"96","author":"GM Buck Louis","year":"2011","unstructured":"Buck Louis GM, Hediger ML, Peterson CM, Croughan M, Sundaram R, Stanford J, et al. 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Due to the explorative character of the study not all ARRIVE guidelines could be implemented from study start, however animal experiments are clearly reported according to the standards set out by the ARRIVE guidelines. The use of human tissues for this study was approved by the ethics committee of the Kantonsspital Baden and participants provided informed written consent. Written and informed consent was obtained from all study participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Endometriosis patients provided informed consent for publication of the images in Fig.\u00a0\n                      \n                      and in Additional file\n                      \n                      : Fig. S5.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MB, VV and RS hold a patent (Patent Number: 11649268) covering the use of fibronectin-binding peptides in the diagnosis and therapy of fibrosis and tumors. IAB is \u201cEditor-in-Chief\u201d of the EJNMMI Res, but was not involved in the review process of this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17"}}