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Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET
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 18F‐misonidazole ([18F]‐FMISO,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423153/ https://www.ncbi.nlm.nih.gov/pubmed/26778791 http://dx.doi.org/10.1016/j.molonc.2015.12.011 |
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author | Hernández-Agudo, Elena Mondejar, Tamara Soto-Montenegro, Maria Luisa Megías, Diego Mouron, Silvana Sanchez, Jesus Hidalgo, Manuel Lopez-Casas, Pedro Pablo Mulero, Francisca Desco, Manuel Quintela-Fandino, Miguel |
author_facet | Hernández-Agudo, Elena Mondejar, Tamara Soto-Montenegro, Maria Luisa Megías, Diego Mouron, Silvana Sanchez, Jesus Hidalgo, Manuel Lopez-Casas, Pedro Pablo Mulero, Francisca Desco, Manuel Quintela-Fandino, Miguel |
author_sort | Hernández-Agudo, Elena |
collection | PubMed |
description | 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 18F‐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. |
format | Online Article Text |
id | pubmed-5423153 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54231532017-08-15 Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET Hernández-Agudo, Elena Mondejar, Tamara Soto-Montenegro, Maria Luisa Megías, Diego Mouron, Silvana Sanchez, Jesus Hidalgo, Manuel Lopez-Casas, Pedro Pablo Mulero, Francisca Desco, Manuel Quintela-Fandino, Miguel Mol Oncol Articles 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 18F‐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. John Wiley and Sons Inc. 2015-12-22 2016-05 /pmc/articles/PMC5423153/ /pubmed/26778791 http://dx.doi.org/10.1016/j.molonc.2015.12.011 Text en © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Hernández-Agudo, Elena Mondejar, Tamara Soto-Montenegro, Maria Luisa Megías, Diego Mouron, Silvana Sanchez, Jesus Hidalgo, Manuel Lopez-Casas, Pedro Pablo Mulero, Francisca Desco, Manuel Quintela-Fandino, Miguel Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET |
title | Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET |
title_full | Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET |
title_fullStr | Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET |
title_full_unstemmed | Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET |
title_short | Monitoring vascular normalization induced by antiangiogenic treatment with 18F‐fluoromisonidazole‐PET |
title_sort | monitoring vascular normalization induced by antiangiogenic treatment with 18f‐fluoromisonidazole‐pet |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423153/ https://www.ncbi.nlm.nih.gov/pubmed/26778791 http://dx.doi.org/10.1016/j.molonc.2015.12.011 |
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