Benjamin Michael Ellingson MS, PhD, Presenter: Research Consultant, MedQIA Imaging Core Laboratory Research Consultant, F. Hoffmann-La Roche Ltd Research Consultant, Tocagen Inc Research Consultant, Boston Scientific Corporation Research Consultant, Amgen Inc Research Grant, Siemens AG Research Grant, F. Hoffmann-La Roche Ltd

Robert Harris, Abstract Co-Author: Nothing to Disclose

Whitney B. Pope MD, PhD, Abstract Co-Author: Research Consultant, F. Hoffmann-La Roche Ltd Research Consultant, Amgen Inc Research Consultant, Tocagen Inc Consultant, Celldex Therapeutics, Inc Consultant, Guerbet SA

Timothy F. Cloughesy MD, Abstract Co-Author: Speakers Bureau, Merck & Co, Inc Consultant, F. Hoffmann-La Roche Ltd Consultant, Merck KGaA Consultant, Novartis AG Consultant, Celgene Corporation

Acidosis is a hallmark of the tumor extracellular microenvironment. Additionally, studies have shown that tumor regions have increased amino acid uptake in order to meet high metabolic demands. Chemical exchange saturation transfer (CEST) MRI is a non-invasive imaging technique that can provide molecular information about the functional groups of molecules. The CEST signal is sensitive to many factors that affect chemical exchange between molecules, including metabolite concentration and pH. In the current study, we develop and test CEST MRI targeted to the amino acid amine group as a pH-weighted imaging biomarker for identifying cancer tissue in patients with various brain tumors.

Samples of glutamine in water at varying pH (4.0 to 8.6 in units of 0.2) were created at varying concentration. Additionally, samples of phenylalanine and glycine were created for the same pH range. CEST data for these samples were collected at 3T on a Siemens Trio scanner (B1=2μT, 15 100-ms RF saturation pulses, 51 spectral points, ± 5.0 ppm). A normalization image was acquired by setting B1=0. Additionally, serial CEST data for a cohort of 12 GBM patients before, during, and after radiochemotherapy. Image-guided biopsies were obtained in an additional two patients with suspected tumor recurrence.

Results show high CEST asymmetry in low pH values between 5.0-7.0 pH and with increasing amino acid concentration. In GBM patients, changes in elevated CEST signal during radiotherapy provided early, independent information regarding the status of the tumor. Some patients showed continual increase in CEST positive regions during therapy, which was followed by early tumor progression (Fig. 1A). In cases of confirmed pseudoprogression, no elevated CEST asymmetry was noted despite an increase in tumor volume on anatomical images (Fig. 1B). Image-guided biopsies of CEST positive locations confirmed tumor, whereas CEST negative regions showed gliosis and little tumor activity.

CEST MRI targeted to the amine protons may provide a pH-weighted imaging biomarker for identifying regions of active tumor proliferation in patients with brain tumors.

A non-invasive imaging method for obtaining tissue pH information would be invaluable as a tool for detecting human cancers and characterizing tumor response to therapy.

Ellingson, B, Harris, R, Pope, W, Cloughesy, T, pH-Weighted Molecular MRI of Human Brain Tumors Using Amine CEST.  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14018693.html