title: Multimodal imaging based on MRI and PET reveals [(18)F]FLT PET as a specific and early indicator of treatment efficacy in a preclinical model of recurrent glioblastoma.
abstract: OBJECTIVE
  The primary objective of this study was to compare the ability of PET and MRI biomarkers to predict treatment efficacy in a preclinical model of recurrent glioblastoma multiforme.
  
  
  METHODS
  MRI (anatomical, diffusion, vasculature and oxygenation) and PET ([(18)F]FDG and [(18)F]FLT) parameters were obtained 3 days after the end of treatment and compared with late tumour growth and survival.
  
  
  RESULTS
  Early after tumour recurrence, no effect of treatment with temozolomide combined with bevacizumab was observed on tumour volume as assessed by T2-W MRI. At later times, the treatment decreased tumour volume and increased survival. Interestingly, at the earlier time, temozolomide + bevacizumab decreased [(18)F]FLT uptake, cerebral blood volume and oedema. [(18)F]FLT uptake, oedema and cerebral blood volume were correlated with overall survival but [(18)F]FLT uptake had the highest specificity and sensitivity for the early prediction of treatment efficacy.
  
  
  CONCLUSIONS
  The present investigation in a preclinical model of glioblastoma recurrence underscores the importance of multimodal imaging in the assessment of oedema, tumour vascular status and cell proliferation. Finally, [(18)F]FLT holds the greatest promise for the early assessment of treatment efficacy. These findings may translate clinically in that individualized treatment for recurrent glioma could be prescribed for patients selected after PET/MRI examinations.
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Corroyer-Dulmont
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Elodie A
authors.initials: EA
authors.lastname: Pérès
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Aurélie N
authors.initials: AN
authors.lastname: Gérault
authors.affiliation: Roche SAS, 30, cours de l'Ile Seguin, 92650, Boulogne-Billancourt, France.
authors.forename: Ariel
authors.initials: A
authors.lastname: Savina
authors.affiliation: Roche SAS, 30, cours de l'Ile Seguin, 92650, Boulogne-Billancourt, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Bouquet
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Divoux
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Toutain
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Méziane
authors.initials: M
authors.lastname: Ibazizène
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Eric T
authors.initials: ET
authors.lastname: MacKenzie
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Louisa
authors.initials: L
authors.lastname: Barré
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France.
authors.forename: Edwige
authors.initials: E
authors.lastname: Petit
authors.affiliation: CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France. valable@cyceron.fr.|CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France. valable@cyceron.fr.|UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France. valable@cyceron.fr.|Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France. valable@cyceron.fr.
authors.forename: Samuel
authors.initials: S
authors.lastname: Valable
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D045744:Cell Line, Tumor; D015224:Dideoxynucleosides; D005909:Glioblastoma / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000188:drug therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D051381:Rats
chemical_list: D015224:Dideoxynucleosides; D019275:Radiopharmaceuticals; C002854:alovudine
keywords: Glioblastoma; Imaging biomarker; MRI; PET; Recurrence; Treatment efficacy