2026-06-14T00:27:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/85372024-11-29T16:42:53Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Hernandez-Agudo, Elena
author
Mondejar, Tamara
author
Soto-Montenegro, Maria Luisa
author
Megias Vazquez, Diego
author
Mouron, Silvana Andrea
author
Sanchez, Jesus
author
Hidalgo, Manuel
author
Lopez-Casas, Pedro Pablo
author
Mulero Francisca, Francisca
author
Desco, Manuel
author
Quintela Fandino, Miguel Angel
funder
Unión Europea
funder
Asociación Española Contra el Cáncer
funder
Ministerio de Sanidad y Consumo (España)
2019-10-30T11:48:43Z
2019-10-30T11:48:43Z
2016-05
Mol Oncol. 2016;10(5):704-18.
10.1016/j.molonc.2015.12.011
1878-0261
15747891
Molecular oncology
26778791
http://hdl.handle.net/20.500.12105/8537
BACKGROUND: 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 (18)F-misonidazole ([18F]-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 [18F]-FMISO-PET, [18F]-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: [18F]-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%). [18F]-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: [18F]-FMISO accurately monitored vascular re-normalization and improved interstitial chemotherapy delivery.
eng
(18)F-misonidazole-PET
Antiangiogenics
Biomarker
Breast cancer
Pancreatic cancer
Vascular normalization
Monitoring vascular normalization induced by antiangiogenic treatment with (18)F-fluoromisonidazole-PET
journal article
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