Aurélien Corroyer-Dulmont1,2,3,4, Elodie A Pérès1,2,3,4, Aurélie N Gérault1,2,3,4, Ariel Savina5, Fanny Bouquet5, Didier Divoux1,2,3,4, Jérôme Toutain1,2,3,4, Méziane Ibazizène1,2,3,4, Eric T MacKenzie1,2,3,4, Louisa Barré1,2,3,4, Myriam Bernaudin1,2,3,4, Edwige Petit1,2,3,4, Samuel Valable6,7,8,9. 1. CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France. 2. CEA, DSV/I2BM, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France. 3. UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France. 4. Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France. 5. Roche SAS, 30, cours de l'Ile Seguin, 92650, Boulogne-Billancourt, France. 6. CNRS, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd H Becquerel, BP 5229, 14074, Caen Cedex, France. valable@cyceron.fr. 7. 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. 8. UNICAEN, UMR 6301 ISTCT, CERVOxy and LDM-TEP groups. GIP CYCERON, Bd Henri Becquerel, BP 5229, 14074, Caen Cedex, France. valable@cyceron.fr. 9. Normandie Univ, Esplanade de la Paix, 14032, Caen Cedex, France. valable@cyceron.fr.
Abstract
PURPOSE: 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. CONCLUSION: 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.
PURPOSE: 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. CONCLUSION: 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.
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