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    188宝金博页面版: [18F]-FMISO PET study of hypoxia in gliomas before surgery： correlation with molecular markers of hypoxia and angiogenesis

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    内容提示： ORIGINAL ARTICLE[18F]-FMISO PETstudy of hypoxia in gliomas before surgery:correlation with molecular markers of hypoxia and angiogenesisLien 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 & Guéna?lle 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 1,2,9Received: 14 November 2016 /Accepted: 9 March 2017 /Publi...

    文档格式：PDF | 页数：10 | 浏览次数：30 | 上传日期：2018-06-22 00:15:53 | 文档星级：
    ORIGINAL ARTICLE[18F]-FMISO PETstudy of hypoxia in gliomas before surgery:correlation with molecular markers of hypoxia and angiogenesisLien 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 1,2,9Received: 14 November 2016 /Accepted: 9 March 2017 /Published online: 18 March 2017# Springer-Verlag Berlin Heidelberg 2017AbstractPurpose Hypoxia in gliomas is associated with tumor resis-tance to radio- and chemotherapy. However, positron emis-siontomography(PET)imagingofhypoxiaremainschalleng-ing, and the validation of biological markers is, therefore, ofgreat importance. We investigated the relationship betweenuptake of the PET hypoxia tracer [18F]-FMISO and othermarkers of hypoxia and angiogenesis and with patientsurvival.Patientsand methods Inthisprospective single centerclinicalstudy, 33 glioma patients (grade IV: n=24, III: n=3, and II:n=6) underwent [18F]-FMISO PETand MRI including rela-tive cerebral blood volume (rCBV) maps before surgery.Maximum standardized uptake values (SUVmax) andhypoxic 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) wereperformed 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), andangiogenesis 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 andSUVmax) and expression of HIF-1α, CAIX, VEGF, Ang2,and rCBV (p<0.01). Patients without [18F]-FMISO uptakehad a longer survival time than uptake positive patients (log-rank, p<0.005).Conclusions Tumor hypoxia as evaluated by [18F]-FMISOPET is associated with the expression of hypoxia markers onamolecularlevelandisrelatedtoangiogenesis.[18F]-FMISOuptake is a mark of an aggressive tumor, almost always aglioblastoma. Our results underline that [18F]-FMISO PETcould be useful to guide glioma treatment, and in particularradiotherapy, since hypoxia is a well-known factor ofresistance.Keywords Hypoxia . [18F]-FMISOPET . Glioma .Glioblastoma . AngiogenesisBackgroundHypoxia is associated with malignant tumor growth, and glio-blastoma (GB), the most frequent primary brain tumor, is aparticularly hypoxic tumor [1]. Upon pathological examina-tion, GB are mainly defined by the presence of necrosis andendothelialproliferation[2].HypoxiainGBisassociatedwith* Lien Bekaertlien.bekaert@gmail.com* Jean-Sébastien Guillamojeansebastien.GUILLAMO@chu-nimes.fr1Department of Neurology, CHU de Caen, Caen, France2Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/CERVOxygroup, 14000 Caen, France3Department of Neurosurgery, CHU de Caen, Caen, France4Service de Neurochirurgie, CHU de Caen, Avenue de la Côte deNacre, 14000 Caen, France5Department of Pathology, CHU de Caen, Caen, France6Department of Neuroradiology, CHU de Caen, Caen, France7Department of Nuclear Medicine, CHU de Caen, Caen, France8Normandie Univ, UNICAEN, CEA, CNRS, ISTCT/LDM-TEPgroup, 14000 Caen, France9Department of Neurology, CHU de Nimes, Place du ProfesseurRobert Debre, 30029 Nimes cedex 9, FranceEur J Nucl Med Mol Imaging (2017) 44:1383–1392DOI 10.1007/s00259-017-3677-5

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