ORIGINAL ARTICLE [18F]-FMISO PET study of hypoxia in gliomas before surgery: correlation with molecular markers of hypoxia and angiogenesis Lien Bekaert 1,2,3,4 & Samuel Valable 2 & Emmanuèle Lechapt-Zalcman 2,5 & Keven Ponte 3,2 & Solène Collet 2 & Jean-Marc Constans 2,6 & Guénaëlle Levallet 5 & Karim Bordji 2 & Edwige Petit 2 & Pierre Branger 1 & Evelyne Emery 3 & Alain Manrique 7 & Louisa Barré 8 & Myriam Bernaudin 2 & Jean-Sébastien Guillamo 1,2,9 Received: 14 November 2016 /Accepted: 9 March 2017 # Springer-Verlag Berlin Heidelberg 2017 Abstract Purpose Hypoxia in gliomas is associated with tumor resis- tance to radio- and chemotherapy. However, positron emis- sion tomography (PET) imaging of hypoxia remains challeng- ing, and the validation of biological markers is, therefore, of great importance. We investigated the relationship between uptake of the PET hypoxia tracer [18F]-FMISO and other markers of hypoxia and angiogenesis and with patient survival. Patients and methods In this prospective single center clinical study, 33 glioma patients (grade IV: n = 24, III: n = 3, and II: n = 6) underwent [18F]-FMISO PET and MRI including rela- tive cerebral blood volume (rCBV) maps before surgery. Maximum standardized uptake values (SUVmax) and hypoxic volume were calculated, defining two groups of pa- tients based on the presence or absence of [18F]-FMISO up- take. After surgery, molecular quantification of CAIX, VEGF, Ang2 (rt-qPCR), and HIF-1α (immunohistochemistry) were performed on tumor specimens. Results [18F]-FMISO PET uptake was closely linked to tu- mor grade, with high uptake in glioblastomas (GB, grade IV). Expression of biomarkers of hypoxia (CAIX, HIF-1α), and angiogenesis markers (VEGF, Ang2, rCBV) were significant- ly higher in the [18F]-FMISO uptake group. We found corre- lations between the degree of hypoxia (hypoxic volume and SUVmax) and expression of HIF-1α, CAIX, VEGF, Ang2, and rCBV (p < 0.01). Patients without [18F]-FMISO uptake had a longer survival time than uptake positive patients (log- rank, p < 0.005). Conclusions Tumor hypoxia as evaluated by [18F]-FMISO PET is associated with the expression of hypoxia markers on a molecular level and is related to angiogenesis. [18F]-FMISO uptake is a mark of an aggressive tumor, almost always a glioblastoma. Our results underline that [18F]-FMISO PET could be useful to guide glioma treatment, and in particular radiotherapy, since hypoxia is a well-known factor of resistance. Keywords Hypoxia . [18F]-FMISO PET . Glioma . Glioblastoma . Angiogenesis Background Hypoxia is associated with malignant tumor growth, and glio- blastoma (GB), the most frequent primary brain tumor, is a particularly hypoxic tumor [1]. Upon pathological examina- tion, GB are mainly defined by the presence of necrosis and endothelial proliferation [2]. Hypoxia in GB is associated with * Lien Bekaert lien.bekaert@gmail.com * Jean-Sébastien Guillamo jeansebastien.GUILLAMO@chu-nimes.fr 1 Department of Neurology, CHU de Caen, Caen, France 2 Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxy group, 14000 Caen, France 3 Department of Neurosurgery, CHU de Caen, Caen, France 4 Service de Neurochirurgie, CHU de Caen, Avenue de la Côte de Nacre, 14000 Caen, France 5 Department of Pathology, CHU de Caen, Caen, France 6 Department of Neuroradiology, CHU de Caen, Caen, France 7 Department of Nuclear Medicine, CHU de Caen, Caen, France 8 Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/LDM-TEP group, 14000 Caen, France 9 Department of Neurology, CHU de Nimes, Place du Professeur Robert Debre, 30029 Nimes cedex 9, France Eur J Nucl Med Mol Imaging DOI 10.1007/s00259-017-3677-5