Intracellular pH measured by 31 P MR-Spectroscopy predicts site of progression in recurrent glioblastoma under antiangiogenic therapy with bevacizumab.
Katharina Johanna Wenger 1 , Oliver Bhr 1 , Elke Hattingen 2 , and Ulrich Pilatus 2
Neurooncology, Goethe-University Frankfurt,
Frankfurt, Hessen, Germany,
Goethe-University Frankfurt, Frankfurt, Hessen, Germany
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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