{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T10:39:55Z","timestamp":1790505595277,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T00:00:00Z","timestamp":1450742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Ministry of Health","award":["FIS PI10\/0288"],"award-info":[{"award-number":["FIS PI10\/0288"]}]},{"name":"Ministry of Health","award":["FIS PI13\/00430"],"award-info":[{"award-number":["FIS PI13\/00430"]}]},{"name":"Ministry of Health","award":["FIS PI 11\/00616"],"award-info":[{"award-number":["FIS PI 11\/00616"]}]},{"name":"Ministry of Health","award":["CPII14\/00005"],"award-info":[{"award-number":["CPII14\/00005"]}]},{"name":"Ministry of Health","award":["FIS PI14\/00860"],"award-info":[{"award-number":["FIS PI14\/00860"]}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:p>\n                    <jats:italic>Background:<\/jats:italic>\n                    Rationalization of antiangiogenics requires biomarkers. Vascular re\u2010normalization is one widely accepted mechanism of action for this drug class. The interstitium of tumors with abnormal vasculature is hypoxic. We sought to track vascular normalization with 18F\u2010misonidazole ([18F]\u2010FMISO, a probe that detects hypoxia) PET, in response to window\u2010of\u2010opportunity (WoO) treatment with the antiangiogenic dovitinib.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Methods:<\/jats:italic>\n                    Two patient\u2010derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV\u2010PyMT were used. Animals were treated during 1 week of WoO treatment with vehicle or dovitinib, preceded and followed by [18F]\u2010FMISO\u2010PET, [18F]\u2010FDG\u2010PET, and histologic assessment (dextran extravasation, hypoxia and microvessel staining, and necrosis, cleaved caspase\u20103 and Ki67 measurements). After WoO treatment, gemcitabine (pancreas)\/adriamycin (breast) or vehicle was added and animals were treated until the humane endpoint. Tumor growth inhibition (TGI) and survival were the parameters studied.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Results:<\/jats:italic>\n                    [18F]\u2010FMISO SUV did not change after dovitinib\u2010WoO treatment compared to vehicle\u2010WoO (0.54 vs. 0.6) treatment in Panc215, but it decreased significantly in Panc286 (0.58 vs. 1.18; P\u00a0&lt;\u00a00.05). In parallel, 10\u2010KDa perivascular dextran extravasation was not reduced with dovitinib or vehicle\u2010WoO treatment in Panc215, but it was reduced in Panc286. Whereas the addition of dovitinib to gemcitabine was indifferent in Panc215, it increased TGI in Panc286 (TGI switched from \u221259% to +49%). [18F]\u2010FMISO SUV changes were accompanied by an almost 100% increase in interstitial gemcitabine delivery (665\u20131260\u00a0ng\/mL). The results were validated in the PyMT model.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusions:<\/jats:italic>\n                    [18F]\u2010FMISO accurately monitored vascular re\u2010normalization and improved interstitial chemotherapy delivery.\n                  <\/jats:p>","DOI":"10.1016\/j.molonc.2015.12.011","type":"journal-article","created":{"date-parts":[[2015,12,22]],"date-time":"2015-12-22T05:56:10Z","timestamp":1450763770000},"page":"704-718","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Monitoring vascular normalization induced by antiangiogenic treatment with 18F\u2010fluoromisonidazole\u2010PET"],"prefix":"10.1002","volume":"10","author":[{"given":"Elena","family":"Hern\u00e1ndez-Agudo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Mondejar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria\u00a0Luisa","family":"Soto-Montenegro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Meg\u00edas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Mouron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Hidalgo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Pablo","family":"Lopez-Casas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Mulero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Desco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Quintela-Fandino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,22]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"1851","article-title":"Assessment of hypoxia and perfusion in human brain tumors using PET with 18F-fluoromisonidazole and 15O-H2O","volume":"45","author":"Bruehlmeier M.","year":"2004","journal-title":"J.\u00a0Nucl. 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