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 [18F]-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 ([18F]-FDG and [18F]-fluoro-l-thymidine [FLT]-PET) studies were undertaken soon (t1) after treatment initiation compared with late anatomical μMRI evaluation of tumor volume (t2) and overall survival. In both models, FDG and FLT uptakes were attenuated at t1 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