Intracellular pH measured by 31 P MR-Spectroscopy predicts site of progression in recurrent glioblastoma under antiangiogenic therapy with bevacizumab.

In solid tumors, major changes in the expression and/or activity of plasma membrane ion pumps and transporters facilitate proton efflux and enable tumor cells to maintain a higher intracellular pH (pHi), while the microenvironment (pHe) is commonly more acidic compared to normal differentiated adult cells. An alkaline pHi supports various mechanisms involved in cellular proliferation and limits apoptosis, therefore promoting cell survival. We proposed that these early changes in pH take place before an MR-detectable recurrence occurs. To prove our hypothesis, we employed in-vivo 31P MR spectroscopic imaging (MRSI) in patients with recurrent glioblastoma (rGBM) before and under antiangiogenetic therapy (bevacizumab, BEV) until tumor progression. According to the predefined criteria by Pope et al. for distant or diffuse tumor progression, 14 patients of our institution were selected based on their tumor progression patterns at time of on-study progression (subsequent tumor). An area of interest for voxel selection on baseline MRSI data was defined retrospectively at the site of the subsequent tumor. The area of interest showed no detectable lesions before BEV on standard MRI sequences. The pHi in the area of interest (subsequent tumor) was significantly higher than the pHi of the contralateral normal appearing tissue (control) (p < 0.001) and similar to the pHi of the existing tumor. Elevated pHi in radiographically normal appearing tissue at baseline can predict the site of subsequent progression in patients with recurrent glioblastoma treated with BEV.

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