title: Carbogen-induced increases in tumor oxygenation depend on the vascular status of the tumor: A multiparametric MRI study in two rat glioblastoma models.
abstract: The alleviation of hypoxia in glioblastoma with carbogen to improve treatment has met with limited success. Our hypothesis is that the eventual benefits of carbogen depend on the capacity for vasodilation. We examined, with MRI, changes in fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent signals in response to carbogen. The analyses were performed in two xenograft models of glioma (U87 and U251) recognized to have different vascular patterns. Carbogen increased fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent signals in contralateral tissues. In the tumor core and peritumoral regions, changes were dependent on the capacity to vasodilate rather than on resting fractional cerebral blood volume. In the highly vascularised U87 tumor, carbogen induced a greater increase in fractional cerebral blood volume and blood oxygen saturation in comparison to the less vascularized U251 tumor. The blood oxygenation level dependent signal revealed a delayed response in U251 tumors relative to the contralateral tissue. Additionally, we highlight the considerable heterogeneity of fractional cerebral blood volume, blood oxygen saturation, and blood oxygenation level dependent within U251 tumor in which multiple compartments co-exist (tumor core, rim and peritumoral regions). Finally, our study underlines the complexity of the flow/metabolism interactions in different models of glioblastoma. These irregularities should be taken into account in order to palliate intratumoral hypoxia in clinical trials.
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Ararat
authors: A
authors: Chakhoyan
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Aurélien
authors: A
authors: Corroyer-Dulmont
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Marine M
authors: MM
authors: Leblond
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Aurélie
authors: A
authors: Gérault
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Jérôme
authors: J
authors: Toutain
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.|5 UMS3408, GIP CYCERON, Caen, France.
authors: Laurent
authors: L
authors: Chazaviel
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Didier
authors: D
authors: Divoux
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Edwige
authors: E
authors: Petit
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Eric T
authors: ET
authors: MacKenzie
authors: 4 Normandie Univ, Esplanade de la Paix, Caen, France.|6 UMR6139 LMNO, Avenue de Côte de Nacre, Caen, France.
authors: François
authors: F
authors: Kauffmann
authors: 3 UNICAEN, GIP CYCERON, Caen, France.|5 UMS3408, GIP CYCERON, Caen, France.
authors: Nicolas
authors: N
authors: Delcroix
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Myriam
authors: M
authors: Bernaudin
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Omar
authors: O
authors: Touzani
authors: 1 CNRS, UMR6301-ISTCT, CERVOxy Group, GIP CYCERON, Caen, France.|2 CEA, DSV/I2BM, GIP CYCERON, Caen, France.|3 UNICAEN, GIP CYCERON, Caen, France.|4 Normandie Univ, Esplanade de la Paix, Caen, France.
authors: Samuel
authors: S
authors: Valable
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000494:pharmacology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005909:Glioblastoma / Q000098:blood supply* / Q000000981:diagnostic imaging; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D010100:Oxygen / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology; D011923:Rats, Nude; D023041:Xenograft Model Antitumor Assays
chemical_list: D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen
keywords: Dynamic blood oxygenation level dependent; fractional cerebral blood volume; glioma; hypoxia; tissue oxygen saturation