Positive Contrast Magnetic Resonance Imaging of Iron Oxide Nanoparticles in Patient-Derived Orthotopic Glioblastoma — The Association Specialists
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Positive Contrast Magnetic Resonance Imaging of Iron Oxide Nanoparticles in Patient-Derived Orthotopic Glioblastoma (21849)

Phillip W Janowicz 1 , Caterina Brighi 1 , Zdenka Kuncic 2 , David EJ Waddington 1
  1. Image X Institute, The University of Sydney, Sydney, New South Wales, Australia
  2. School of Physics, The University of Sydney, Sydney, New South Wales, Australia

Glioblastoma is the most common and aggressive brain cancer in adults, and spreads in an infiltrative manner into healthy brain tissue. We have evaluated superparamagnetic iron oxide nanoparticles (SPIONs) for the magnetic resonance imaging of glioblastoma infiltrate. Antibody-coated and untargeted ‘stealth’ SPIONs were imaged in orthotopic patient-derived xenografts (RN1) which maintain the closed blood brain barrier seen in patients, as well as in U87MG cell-line xenografts which have a relatively permeable blood barrier. The appropriate nanoparticle dose range, pharmacokinetic properties and susceptibility gradient maps for glioblastoma angiogenesis distinction, were evaluated. Moreover, susceptibility gradient mapping allowed the T2 (dark) nanoparticle contrast to be viewed as a sensitive positive (bright) contrast.  Interestingly, the untargeted stealth SPIONs exhibited longer blood circulation times compared to the human IgG1 targeted SPIONs, by avoiding rapid reticuloendothelial blood clearance. These GMP-grade stealth SPIONs could potentially be a clinical advancement over the conventionally used gadolinium-based contrast agents by avoiding toxicity, especially in patients susceptible to nephrogenic systemic fibrosis. The nanoparticles and imaging methods used in this study could also potentially be applied to other brain malignancies such as metastases, and peripheral tumours.