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Baseline CEUS with VEGFR2-targeted microbubbles was performed on day 7. The therapy group received intraperitoneal anti-PD-L1 and anti-CTLA-4 antibodies between days 7\u201315; controls received sham treatment. Follow-up CEUS was performed on days 14 and 21. Tumor perfusion (WiAUC) and VEGFR2 binding (SI\n                      <jats:sub>8min<\/jats:sub>\n                      , SI\n                      <jats:sub>10min<\/jats:sub>\n                      ) were quantified, and immunohistochemistry assessed CD8, Ki-67, TUNEL, CD31, and VEGFR2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At FU1, WiAUC was significantly lower in the therapy group compared with controls (4,029\u2009\u00b1\u200961 vs. 6,391\u2009\u00b1\u2009412;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and remained significantly lower at FU2 (1,028\u2009\u00b1\u200927 vs. 2,049\u2009\u00b1\u200939;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). VEGFR2-targeted microbubble binding was consistently lower under therapy. At FU1, SI\n                      <jats:sub>8min<\/jats:sub>\n                      was 407\u2009\u00b1\u200911 vs. 626\u2009\u00b1\u200913 and SI\n                      <jats:sub>10min<\/jats:sub>\n                      was 409\u2009\u00b1\u200910 vs. 634\u2009\u00b1\u200928 (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). At FU2, SI\n                      <jats:sub>8min<\/jats:sub>\n                      was 106\u2009\u00b1\u20096 vs. 207\u2009\u00b1\u20094 and SI\n                      <jats:sub>10min<\/jats:sub>\n                      was 107\u2009\u00b1\u20095 vs. 207\u2009\u00b1\u20094 (both\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Immunohistochemistry confirmed higher apoptosis and tumor-infiltrating lymphocytes, and lower proliferation, microvascular density, and VEGFR2 expression in treated tumors (all\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>VEGFR2-targeted CEUS enabled longitudinal monitoring of early response to dual anti-PD-L1\/anti-CTLA-4 immunotherapy in colorectal cancer. Treated tumors showed lower perfusion and VEGFR2-targeted binding, paralleled by reduced vessel density and VEGFR2 expression as well as increased CD8 infiltration and apoptosis. These findings support VEGFR2-targeted CEUS as a promising noninvasive imaging biomarker for monitoring early immunotherapy-associated vascular changes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40644-026-01101-0","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:53:39Z","timestamp":1785509619000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CEUS with VEGFR2-targeted microbubbles for monitoring of early immunotherapy effects in a colorectal cancer model"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0835-0328","authenticated-orcid":false,"given":"Felix L.","family":"Herr","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan K.","family":"Stock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena Gr\u00e4fin zu","family":"Solms-Baruth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larissa V.","family":"Blume","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Kloiber-Langhorst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidrun","family":"Hirner-Eppeneder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Stueckl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Akla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Ricke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Geyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Kunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice M.","family":"Heimer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk-Andre","family":"Clevert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa J.","family":"Antons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens C.","family":"Cyran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"issue":"26","key":"1101_CR1","doi-asserted-by":"publisher","first-page":"2509","DOI":"10.1056\/NEJMoa1500596","volume":"372","author":"DT Le","year":"2015","unstructured":"Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA. 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All other authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"94"}}