Intracellular pH measured by31P-MR-spectroscopy might predict site of progression in recurrent glioblastoma under antiangiogenic therapy.
In solid tumors, changes in the expression/activity of plasma membrane ion transporters facilitate proton efflux and enable tumor cells to maintain a higher intracellular pH (pHi), while the microenvironment (pHe) is commonly more acidic. This supports various tumor-promoting mechanisms. We propose that these changes in pH take place before a magnetic resonance imaging (MRI)-detectable brain tumor recurrence occurs.



We enrolled 66 patients with recurrent glioblastoma, treated with bevacizumab. Patients received a baseline and 8-week follow-up MRI including1H/31P MRSI (spectroscopy) on a 3T clinical scanner, until progressive disease according to Response Assessment in Neuro-Oncology (RANO) criteria occurred. Fourteen patients showed a distant or diffuse tumor recurrence (subsequent tumor) during treatment and were therefore selected for further evaluation. At the site of the subsequent tumor, an area of interest for MRSI voxel selection was retrospectively defined on radiographically unaffected baseline MRI sequences.



Before treatment, pHiin the area of interest (subsequent tumor) was significantly higher than pHiof the contralateral normal-appearing tissue (control; P < 0.001). It decreased at the time of best response (P = 0.06), followed by a significant increase at progression (P = 0.03; baseline mean: 7.06, median: 7.068, SD: 0.032; best response mean: 7.044, median: 7.036, SD: 0.025; progression mean: 7.08, median: 7.095, SD 0.035). Until progression, the subsequent tumor was not detectable on standard MRI sequences. The area of existing tumor responded similar, but changes were not significant (decrease P = 0.22; increase P = 0.28).



Elevated pHiin radiographically unaffected tissue at baseline might precede MRI-detectable progression in patients with recurrent glioblastoma treated with bevacizumab.



2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1200-1208.
Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Katharina J
KJ
Wenger
Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
Elke
E
Hattingen
Department of Neurosurgery, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
Kea
K
Franz
Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Joachim P
JP
Steinbach
Dr. Senckenberg Institute of Neurooncology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.|German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Oliver
O
Bähr
Institute of Neuroradiology, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
Ulrich
U
Pilatus
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000737:chemistry / Q000188:drug therapy*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000737:chemistry* / Q000175:diagnosis; D010758:Phosphorus; D011446:Prospective Studies
D020533:Angiogenesis Inhibitors; D010758:Phosphorus; D000068258:Bevacizumab
31P-MR-spectroscopy; bevacizumab; glioblastoma; pHi; tumor progression