title: MRI monitoring of monocytes to detect immune stimulating treatment response in brain tumor.
abstract: Glioblastoma (GBM) is an aggressive brain cancer with a poor prognosis. The use of immune therapies to treat GBM has become a promising avenue of research. It was shown that amphotericin B (Amp B) can stimulate the innate immune system and suppress the growth of brain tumor initiating cells (BTICs). However, it is not feasible to use histopathology to determine immune activation in patients. We developed an MRI technique that can rapidly detect a therapeutic response in animals treated with drugs that stimulate innate immunity. Ultra-small iron oxide nanoparticles (USPIOs) are MRI contrast agents that have been widely used for cell tracking. We hypothesized that the increased monocyte infiltration into brain tumors due to Amp B can be detected using USPIO-MRI, providing an indicator of early drug response.
  
  
  
  We implanted human BTICs into severe combined immunodeficient mice and allowed the tumor to establish before treating the animals with either Amp B or vehicle and then imaged them using MRI with USPIO (ferumoxytol) contrast.
  
  
  
  After 7 days of treatment, there was a significantly decreased T2* in the tumor of Amp B but not vehicle animals, suggesting that USPIO is carried into the tumor by monocytes. We validated our MRI results with histopathology and confirmed that Amp B-treated animals had significantly higher levels of macrophage/microglia that were colocalized with iron staining in their brain tumor compared with vehicle mice.
  
  
  
  USPIO-MRI is a promising method of rapidly assessing the efficacy of anticancer drugs that stimulate innate immunity.
authors: Department of Radiology, University of Calgary, Calgary, Alberta, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
authors: Runze
authors: R
authors: Yang
authors: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
authors: Susobhan
authors: S
authors: Sarkar
authors: Department of Radiology, University of Calgary, Calgary, Alberta, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
authors: Daniel J
authors: DJ
authors: Korchinski
authors: Department of Radiology, University of Calgary, Calgary, Alberta, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
authors: Ying
authors: Y
authors: Wu
authors: Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.|Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
authors: V Wee
authors: VW
authors: Yong
authors: Department of Radiology, University of Calgary, Calgary, Alberta, Canada.|Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.|Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
authors: Jeff F
authors: JF
authors: Dunn
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D058948:Cell Tracking / Q000379:methods*; D003287:Contrast Media / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D016513:Mice, SCID; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000900:Anti-Bacterial Agents; D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D000666:Amphotericin B
keywords: drug response; glioblastoma; innate immunity; iron oxide; MRI