title: Detection of glioblastoma response to temozolomide combined with bevacizumab based on μMRI and μPET imaging reveals [18F]-fluoro-L-thymidine as an early and robust predictive marker for treatment efficacy.
abstract: The individualized care of glioma patients ought to benefit from imaging biomarkers as precocious predictors of therapeutic efficacy. Contrast enhanced MRI and [(18)F]-fluorodeoxyglucose (FDG)-PET are routinely used in clinical settings; their ability to forecast the therapeutic response is controversial. The objectives of our preclinical study were to analyze sensitive µMRI and/or µPET imaging biomarkers to predict the efficacy of anti-angiogenic and/or chemotherapeutic regimens. Human U87 and U251 orthotopic glioma models were implanted in nude rats. Temozolomide and/or bevacizumab were administered. µMRI (anatomical, diffusion, and microrheological parameters) and µPET ([(18)F]-FDG and [(18)F]-fluoro-l-thymidine [FLT]-PET) studies were undertaken soon (t(1)) after treatment initiation compared with late anatomical µMRI evaluation of tumor volume (t(2)) and overall survival. In both models, FDG and FLT uptakes were attenuated at t(1) in response to temozolomide alone or with bevacizumab. The distribution of FLT, reflecting intratumoral heterogeneity, was also modified. FDG was less predictive for treatment efficacy than was FLT (also highly correlated with outcome, P < .001 for both models). Cerebral blood volume was significantly decreased by temozolomide + bevacizumab and was correlated with survival for rats with U87 implants. While FLT was highly predictive of treatment efficacy, a combination of imaging biomarkers was superior to any one alone (P < .0001 in both tumors with outcome). Our results indicate that FLT is a sensitive predictor of treatment efficacy and that predictability is enhanced by a combination of imaging biomarkers. These findings may translate clinically in that individualized glioma treatments could be decided in given patients after PET/MRI examinations.
authors.affiliation: CNRS, UMR ISTCT 6301, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP5229, 14074 CAEN cedex, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Corroyer-Dulmont
authors.forename: Elodie A
authors.initials: EA
authors.lastname: Pérès
authors.forename: Edwige
authors.initials: E
authors.lastname: Petit
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Guillamo
authors.forename: Nathalie
authors.initials: N
authors.lastname: Varoqueaux
authors.forename: Simon
authors.initials: S
authors.lastname: Roussel
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.forename: Didier
authors.initials: D
authors.lastname: Divoux
authors.forename: Eric T
authors.initials: ET
authors.lastname: MacKenzie
authors.forename: Jérôme
authors.initials: J
authors.lastname: Delamare
authors.forename: Méziane
authors.initials: M
authors.lastname: Ibazizène
authors.forename: Myriam
authors.initials: M
authors.lastname: Lecocq
authors.forename: Andréas H
authors.initials: AH
authors.lastname: Jacobs
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.forename: Samuel
authors.initials: S
authors.lastname: Valable
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D015415:Biomarkers / Q000032:analysis; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019788:Fluorodeoxyglucose F18; D005909:Glioblastoma / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats; D011923:Rats, Nude; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D000068258:Bevacizumab; D003606:Dacarbazine; D000077204:Temozolomide