Imaging glioblastoma pH using CEST-MRI

• Research type

  Research Study

• Full title

  A single arm exploratory study examining the feasibility of imaging glioblastoma pH using CEST-MRI

• IRAS ID

  226840

• Contact name

  Simon Lord

• Contact email

  simon.lord@oncology.ox.ac.uk

• Sponsor organisation

  University of Oxford

• Duration of Study in the UK

  1 years, 2 months, 17 days

• Research summary

  Research Summary
  Several studies have demonstrated that acidity within tumours is greater that in normal tissue. This effect is predominantly driven by the hypoxic (low oxygen) environment in the tumour cells, and accumulation of lactic/carboxylic acid as the cells generate energy in the absence of oxygen. Extracellular acidity has been linked to increased tumour invasion and angiogenesis (blood vessel formation), reduced immune function and also resistance to radiation and systemic cytotoxic (anti-cancer drug) therapy.\n\nChemical exchange saturation transfer (CEST) MRI is a non-invasive imaging technique that can give a readout of tissue pH (acidity). Besides pH there is evidence that this technique is also sensitive to protein concentration in tumour models. This technique is already being assessed in stroke patients to aid the detection of areas with restricted blood supply and there is also a preclinical program in Oxford to develop this technique to evaluate tumours.\n\nThe primary objective for this study is to evaluate CEST contrast image obtained from CEST MRI in glioblastoma, a type of brain cancer. As part of this study there are also several exploratory objectives in which the CEST-MRI signature will be correlated with tissue perfusion using arterial spin labelling/ASL perfusion MRI (a non-invasive imaging technique which assesses tissue perfusion/the extent of water and nutrient exchange with tissue) and tissue based testing including pH, protein content and immunohistochemistry to assess for hypoxia markers.\n\nStudy participants (previously untreated glioblastoma patients for resection/debulking surgery) will undergo a CEST-MRI scan and ASL Perfusion MRI scan in addition to their standard care anatomical MRI scan. These may be repeated at the next standard care imaging visit if there are concerns over the time period between imaging and surgery. At surgery, biopsies will be taken for analysis prior to tumour resection/debulking. No visits additional to standard care are anticipated.\n

  Summary of Results
  IMAGO was a single-armed, exploratory clinical trial that was designed to investigate whether a new form of cancer scan called Amide-CEST-MRI might be useful in imaging glioblastoma, a type of brain tumour. Due to low oxygen supply glioblastoma tumours are often acidic and Amide-CEST-MRI scans are thought to be able to pick up acidic areas in tissue.
  The primary objective of IMAGO was to evaluate CEST contrast images obtained from CEST MRI in glioblastoma by assessing pH weighted CEST MRI signal using amide proton transfer ratio analysis. The study was carried out by the University of Oxford and funded by the Cancer Imaging Centre Oxford (CICO) (jointly funded by Cancer Research UK and the Engineering and Physical Sciences Research Council).
  The target population in the study were adult glioblastoma patients scheduled for resection or debulking (a type of surgery) and who would be willing and able to comply with protocol requirements and be able to provide informed consent. Participants were asked to undergo research tests on two separate occasions. Both sets of research tests took place on visits when the patients were scheduled for standard of care tests or their planned surgery, so no additional hospital visits were required.
  In total 20 participants were recruited to the study. After providing consent, participants underwent a CEST-MRI scan and ASL Perfusion MRI which was combined with their standard of care MRI brain scan, typically within 28 days of planned surgery. 0-4 weeks later, patients would undergo their surgery to remove or debulk the glioblastoma brain tissue. During the procedure, the neurosurgeon used images taken during MRI scans to guide and take biopsies from the glioblastoma tumour. Samples used for IMAGO were taken from the tumour during planned surgery, so there was no additional risk to the patient. IMAGO samples were subsequently analysed for acidity, oxygen levels and protein concentration at Oxford University laboratories. Data from samples was compared with signals seen from the MRI scans.
  The study observed that there were higher ‘Amide-CEST’ levels in the tumours suggesting potential for this type of scan as a way of imaging glioblastoma. Further work is ongoing to explore what Amide-CEST-MRI might tell us about the ‘biology’ of the cancer, for example how it might inform doctors as to what treatment to use. IMAGO results are planned to be published in a peer reviewed journal.

• REC name

  South Central - Oxford A Research Ethics Committee

• REC reference

  17/SC/0304

• Date of REC Opinion

  18 Jul 2017

• REC opinion

  Favourable Opinion