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Ga-68 labeling of D0103 was done manually for preclinical experiments and fully automated for clinical application. Preclinical characterization of Ga-68-D0103 was performed in SCID mice bearing subcutaneous xenografts of H2009 (\u03b1v\u03b26-positive) or MDA-MB-231 (\u03b1v\u03b26-negative) carcinoma cell lines, by ex vivo biodistribution (10, 30, 90, and 180\u00a0min p.i) and PET imaging (30, 90, and 180\u00a0min p.i.)., without and with co-injection of gelofusine (4% succinylated gelatin). A patient with type-II diabetes (f, 68y, 115\u00a0kg) with proximal G2 ESCC was investigated by Ga-68-D0103 PET\/CT (193\u00a0MBq) at 15, 45, 90, and 104\u00a0min p.i..<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>99% of ESCC cases were found \u03b26-integrin positive by IHC, of which 48%, 31%, and 20% showed strong, moderate, and low ITGB6 expression, respectively, with no correlation to tumor grade. Ex vivo biodistribution of Ga-68-D0103 in H2009 xenografted mice after 30, 90, and 180\u00a0min showed tumor-to-blood ratios of 6.8, 37, and 124, respectively; tumor-to-muscle ratios of 12, 14, and 36, respectively; tumor-to-liver ratios of 10, 17, and 14, respectively; and tumor-to-pancreas ratios of 20, 47, and 56, respectively. Co-administration of gelofusine did not change the tumor uptake but reduced the kidney uptake by 89% (from 178%iA\/g to 19.1%iA\/g, 90\u00a0min p.i.), resulting in an 8.7-fold higher tumor\/kidney ratio. \u00b5PET imaging in H2009 xenografted mice confirmed a high tumor uptake and low background already 30\u00a0min p.i.. Blockade biodistribution and \u00b5PET in \u03b1v\u03b26-(\u2013) MDA-MB-231 mice demonstrated target specificity. Clinical PET\/CT of a patient with ESCC showed increasing tracer uptake over time in the primary tumor (SUVmax 9.0 and 11.3 at 15 and 104\u00a0min p.i., respectively) and in a lymph node metastasis (SUVmax 19.5 and 28.3, respectively), and a decreasing blood pool activity (SUVmean 2.75 and 0.98, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>High (99%) membranous expression frequency and density on tumor cells underscores the potential of \u03b1v\u03b26-integrin as a theranostic target in ESCC, suggesting that \u03b1v\u03b26-integrin PET\/CT imaging may adopt a role in re-staging and therapy guidance in this cancer type. The prolonged tumor retention furthermore indicates a therapeutic potential of \u03b1v\u03b26-integrin targeted radiopharmaceuticals when labeled with radionuclides such as lutetium-177, terbium-161, or actinium-225.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-025-07408-7","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T23:54:45Z","timestamp":1750377285000},"page":"607-618","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["PET\/CT imaging of esophageal cancer targeting tumor cell specific \u03b1v\u03b26-integrin expression"],"prefix":"10.1007","volume":"53","author":[{"given":"Kate\u0159ina Dvo\u0159\u00e1kov\u00e1","family":"Bendov\u00e1","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Groll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Neu\u017eilov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krist\u00fdna","family":"Krasulov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zbyn\u011bk","family":"Nov\u00fd","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Falco","family":"Reissig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katja","family":"Steiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Boxberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Eppard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Wuestemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mari\u00e1n","family":"Hajd\u00fach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moritz","family":"Jesinghaus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"\u0160ime\u010dek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael C.","family":"Kreissl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milo\u0161","family":"Pet\u0159\u00edk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-3391","authenticated-orcid":false,"given":"Johannes","family":"Notni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,6,20]]},"reference":[{"key":"7408_CR1","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/s41568-018-0038-z","volume":"18","author":"H Hamidi","year":"2018","unstructured":"Hamidi H, Ivaska J. 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