Publication:
Monitoring vascular normalization induced by antiangiogenic treatment with F-18-fluoromisonidazole-PET

Simple item page
dc.affiliation.dptoUC3M. Departamento de Bioingenieríaes
dc.affiliation.grupoinvUC3M. Grupo de Investigación: Biomedical Imaging and Instrumentation Groupes
dc.contributor.authorHernandez Agudo, Elena
dc.contributor.authorMondejar, Tamara
dc.contributor.authorSoto Montenegro, Mª Luisa
dc.contributor.authorMegias, Diego
dc.contributor.authorMouron, Silvana
dc.contributor.authorSanchez, Jesus
dc.contributor.authorHidalgo, Manuel
dc.contributor.authorLopez Casas, Pedro Pablo
dc.contributor.authorMulero, Francisca
dc.contributor.authorDesco Menéndez, Manuel
dc.contributor.authorQuintela Fandino, Miguel
dc.date.accessioned2023-10-31T13:37:41Z
dc.date.available2023-10-31T13:37:41Z
dc.date.issued2016-05
dc.description.abstractBackground: Rationalization of antiangiogenics requires biomarkers. Vascular re normalization 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 F-18-misonidazole ([F-18]-FMISO, a probe that detects hypoxia) PET, in response to window-of-opportunity (WoO) treatment with the antiangiogenic dovitinib. Methods: Two patient-derived pancreas xenografts (PDXs; Panc215 and Panc286) and the spontaneous breast cancer model MMTV-PyMT were used. Animals were treated during 1 week of WoO treatment with vehicle or dovitinib, preceded and followed by [F-18]-FMISO-PET, [F-18]-FDG-PET, and histologic assessment (dextran extravasation, hypoxia and microvessel staining, and necrosis, cleaved caspase-3 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. Results: [F-18]-FMISO SUV did not change after dovitinib-WoO treatment compared to vehicle-WoO (0.54 vs. 0.6) treatment in Panc215, but it decreased significantly in Panc286 (0.58 vs. 1.18; P < 0.05). In parallel, 10-KDa perivascular dextran extravasation was not reduced with dovitinib or vehicle-WoO 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 -59% to +49%). [F-18]-FMISO SUV changes were accompanied by an almost 100% increase in interstitial gemcitabine delivery (665-1260 ng/mL). The results were validated in the PyMT model. Conclusions: [F-18]-FMISO accurately monitored vascular re-normalization and improved interstitial chemotherapy delivery.en
dc.description.sponsorshipThis work was supported by the following sources: Fondo de Investigación Sanitaria (Ministry of Health, Spain; numbers FIS PI10/0288, FIS PI13/00430, FIS PI 11/00616, CPII14/00005 and FIS PI14/00860; the first two awarded to MQF and the last three to MD), and "Fondo Europeo de Desarrollo Regional (FEDER) - Una manera de hacer Europa". MQF is a recipient of a 2010 Beca-Retorno from the AECC Scientific Foundation. Rosae Foundation and AVON España S.A.U. contributed to this work with unrestricted donations. Dovitinib was kindly provided by Novartis.en
dc.format.extent15
dc.identifier.bibliographicCitationHernández-Agudo, E., Mondejar, T., Soto-Montenegro, M. L., Megı́as, D., Mourón, S., Sanchez, J. M., Hidalgo, M., López-Casas, P. P., Mulero, F., Desco, M., & Quintela-Fandiño, M. (2016). Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET. Molecular Oncology, 10(5), 704-718. hen
dc.identifier.doihttps://doi.org/10.1016/j.molonc.2015.12.011
dc.identifier.issn1878-0261
dc.identifier.publicationfirstpage704
dc.identifier.publicationissue5
dc.identifier.publicationlastpage718
dc.identifier.publicationtitleMolecular Oncologyen
dc.identifier.publicationvolume10
dc.identifier.urihttps://hdl.handle.net/10016/38724
dc.identifier.uxxiAR/0000018071
dc.language.isoengen
dc.publisherFEBS Pressen
dc.rights© 2016 The Authors.en
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 España*
dc.rights.accessRightsopen accessen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/es/*
dc.subject.ecienciaBiología y Biomedicinaes
dc.subject.ecienciaElectrónicaes
dc.subject.ecienciaInformáticaes
dc.subject.ecienciaMedicinaes
dc.subject.ecienciaTelecomunicacioneses
dc.subject.otherAntiangiogenicsen
dc.subject.otherVascular normalizationen
dc.subject.otherBiomarkeren
dc.subject.otherF-18-misonidazole-peten
dc.subject.otherPancreatic canceren
dc.subject.otherBreast canceren
dc.titleMonitoring vascular normalization induced by antiangiogenic treatment with F-18-fluoromisonidazole-PETen
dc.typeresearch article*
dc.type.hasVersionVoR*
dspace.entity.typePublication
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Monitoring_MO_2016.pdf
Size:
4.77 MB
Format:
Adobe Portable Document Format
Download
Collections
DBIAB - BIIG - Journal Articles