title: A pilot study using dynamic contrast enhanced-MRI as a response biomarker of the radioprotective effect of memantine in patients receiving whole brain radiotherapy.
abstract: This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT).
  
  
  
  14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient's ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry.
  
  
  
  Following WBRT, there was an increasing trend in the vascular permeability of tumors (p=0.09) and NAWM (p=0.06) with time. Memantine significantly (p=0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p= 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use.
  
  
  
  DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.
authors.affiliation: Department of Radiation Oncology, Centre Hospitalier de L'Université de Montréal, Montréal, Québec, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Wong
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Ilana R
authors.initials: IR
authors.lastname: Leppert
authors.affiliation: Department of Radiation Oncology, Centre Hospitalier de L'Université de Montréal, Montréal, Québec, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Roberge
authors.affiliation: Department of Radiation Oncology, Centre Hospitalier de L'Université de Montréal, Montréal, Québec, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Boudam
authors.affiliation: Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States of America.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Brown
authors.affiliation: Department of Oncology, Jewish General Hospital, Montreal, Québec, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Muanza
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.|Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada.
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Pike
authors.affiliation: Diagnostic Radiology, McGill University Health Center, Montréal, Québec, Canada.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chankowsky
authors.affiliation: Department of Oncology, McGill University Health Center, Montreal, Québec, Canada.
authors.forename: Catalin
authors.initials: C
authors.lastname: Mihalcioiu
mesh_terms: D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000528:radiation effects; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000556:secondary; D002199:Capillary Permeability; D003287:Contrast Media; D016371:Cranial Irradiation / Q000009:adverse effects; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D008875:Middle Aged; D010865:Pilot Projects; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*
chemical_list: D003287:Contrast Media; D011837:Radiation-Protective Agents; D008559:Memantine
keywords: MRI; biomarker; imaging; memantine; radiotherapy