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Vascular adhesion protein-1 (VAP-1) is an endothelial cell surface molecule that controls leukocyte extravasation into sites of inflammation. However, the role of inflammation-induced VAP-1 expression in IBD is still unclear. Therefore, this study investigated the utility of VAP-1-targeted [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Siglec-9 positron emission tomography\/computed tomography (PET\/CT) for assessing inflammation in two mouse models of IBD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedures<\/jats:title>\n                    <jats:p>\n                      Studies were performed using K8\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      mice that develop a chronic colitis-phenotype and C57Bl\/6NCrl mice with acute intestinal inflammation chemically-induced using 2.5% dextran sodium sulfate (DSS) in drinking water. In both diseased and control mice, uptake of the VAP-1-targeting peptide [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Siglec-9 was assessed in intestinal regions of interest using\n                      <jats:italic>in vivo<\/jats:italic>\n                      PET\/CT, after which\n                      <jats:italic>ex vivo<\/jats:italic>\n                      gamma counting, digital autoradiography, and histopathological analyses were performed. Immunofluorescence staining was performed to determine VAP-1-expression in the intestine, including in samples from patients with ulcerative colitis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Intestinal inflammation could be visualized by [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Siglec-9 PET\/CT in two murine models of IBD. In both models, the\n                      <jats:italic>in vivo<\/jats:italic>\n                      PET\/CT and\n                      <jats:italic>ex vivo<\/jats:italic>\n                      studies of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Siglec-9 uptake were significantly higher than in control mice. The\n                      <jats:italic>in vivo<\/jats:italic>\n                      uptake was increased on average 1.4-fold in the DSS model and 2.0-fold in the K8\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      model. Immunofluorescence staining revealed strong expression of VAP-1 in the inflamed intestines of both mice and patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study suggests that the VAP-1-targeting [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Siglec-9 PET tracer is a promising tool for non-invasive imaging of intestinal inflammation. Future studies in patients with IBD and evaluation of the potential value of [\n                      <jats:sup>68<\/jats:sup>\n                      Ga]Ga-DOTA-Siglec-9 in diagnosis and monitoring of the disease are warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11307-023-01885-8","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T16:47:46Z","timestamp":1702918066000},"page":"322-333","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Detection of Intestinal Inflammation by Vascular Adhesion Protein-1-Targeted [68Ga]Ga-DOTA-Siglec-9 Positron Emission Tomography in Murine Models of Inflammatory Bowel Disease"],"prefix":"10.1007","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1491-5899","authenticated-orcid":false,"given":"Achol A.","family":"Bhowmik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taina R. 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The remaining authors have no competing interests to disclose.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of Interest"}},{"value":"All animal experiments were approved by the national Project Authorization Board in Finland (licenses ESAVI\/16359\/2019 and ESAVI\/8648\/2020) and were carried out in compliance with the ARRIVE guidelines. Human intestinal samples were from patients with UC participating in a clinical trial approved by the joint Ethics Committee of the University of Turku and Turku University Hospital (CLN9801, ethics approval 31.3.1998 \u00a776, and amendment CLN9901 16.3.1999 \u00a797).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical Approval and Consent to Participate"}}]}}