pH-weighted amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) as a potential early biomarker for bevacizumab failure in recurrent glioblastoma.

Purpose: The objective of the current study was to explore the efficacy of using pH-weighted amine CEST-EPI as a potential non-invasive imaging biomarker for treatment response and/or failure in recurrent GBM patients treated with bevacizumab.
Method: A total of 11 patients with recurrent GBM treated with bevacizumab were included in this prospective study. CEST-EPI, perfusion MRI, and standardized anatomic MRI were obtained in patients before and after bevacizumab administration. CEST-EPI measures of magnetization transfer ratio asymmetry (MTR _asym ) at 3 ppm were used for pH-weighted imaging contrast. Multiple measures were examined for their association with progression-free survival (PFS).
Result: Tumor acidity, measured with MTR _asym at 3 ppm, was significantly reduced in both contrast enhancing and non-enhancing tumor after bevacizumab (p = 0.0002 and p < 0.00001, respectively). The reduction in tumor acidity in both contrast enhancing and non-enhancing tumor was linearly correlated with PFS (p = 0.044 and p = 0.00026, respectively). In 9 of the 11 patients, areas of residual acidity were localized to areas of tumor recurrence, typically around 2 months prior to radiographic progression. Univariate (p = 0.006) and multivariate Cox regression controlling for age (p = 0.009) both indicated that change in tumor acidity (ΔMTR _asym at 3 ppm) was a significant predictor of PFS.
Conclusions: This pilot study suggests pH-weighted amine CEST MRI may have value as a non-invasive, early imaging biomarker for bevacizumab treatment response and failure. Early decreases MTR _asym at 3.0 ppm in recurrent GBM after bevacizumab may be associated with better PFS. Residual or emerging regions of acidity may colocalize to the site of tumor recurrence.