Childhood Cancer Data Initiative Annual Symposium (Abstract Registration): Submission #39

serial: '39'
sid: '148272'
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uri: /nci/ccdisymposium/abstract
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langcode: en
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data:
  authors_:
    - add_author_degree: Ph.D.
      add_author_first_name: 'Saikat '
      add_author_last_name: Maiti
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: B.Sc.
      add_author_first_name: Maya
      add_author_last_name: Teitz
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: B.Sc.
      add_author_first_name: Esteban
      add_author_last_name: Velarde
      add_author_middle: ''
      add_author_organization: 'Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231'
    - add_author_degree: Ph.D.
      add_author_first_name: Xiaoju
      add_author_last_name: Yang
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: B.SC.
      add_author_first_name: Shana
      add_author_last_name: Lee
      add_author_middle: ''
      add_author_organization: 'Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205'
    - add_author_degree: B.Sc.
      add_author_first_name: Kristen
      add_author_last_name: Lecksell
      add_author_middle: ''
      add_author_organization: 'Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: B.Sc.
      add_author_first_name: Barbara
      add_author_last_name: Smith
      add_author_middle: J.
      add_author_organization: 'Department of Cell Biology, Baltimore, MD 21205'
    - add_author_degree: Ph.D.
      add_author_first_name: Anupama
      add_author_last_name: Kumari
      add_author_middle: ''
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287'
    - add_author_degree: Ph.D.
      add_author_first_name: Adnan
      add_author_last_name: Bibic
      add_author_middle: ''
      add_author_organization: 'F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205'
    - add_author_degree: Ph.D.
      add_author_first_name: Ethel
      add_author_last_name: Ngen
      add_author_middle: J.
      add_author_organization: 'Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287; Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21287  '
  abstract: |
    Introduction: Radiotherapy-induced brain injury (RIBI) affects up to 90% of brain tumor survivors treated with radiotherapy. Thus, there is a need for RIBI therapeutic strategies. 

    Hypothesis: Oxidative stress and neuroinflammation are key contributors to RIBI. Thus, therapies that reduce oxidative stress and neuroinflammation could mitigate RIBI. 

    Objective: Two redox-responsive nanotheranostic agents were developed and evaluated in a preclinical mouse model of RIBI.

    Method: Two agents (P2a and P2b) with varying numbers of phenylboronic acid pinacol ester (BAPE) moieties to scavenge reactive oxygen species (ROS) were developed and characterized. The agents were next intravenously injected (IV) into mice at two weeks post-irradiation, as follows: Group 1 [phosphate buffered saline (PBS)]; Group 2 (P2a); Group 3 (P2b). The mice were then monitored with fluorescence imaging; magnetic resonance imaging (MRI) and immunohistochemistry.

    Results: Both agents accumulated in the irradiated region of the mouse brain 4 h post-IV and were retained for 7 days. Contrast-enhanced T1W MRI, 1.5 months post-IV, showed significantly reduced disruption of the blood brain barrier in mice treated with P2b compared to PBS and P2a. T2W MRI also showed significantly reduced edema/astrogliosis in mice treated with P2b and P2a, compared to PBS. Immunohistochemistry confirmed significantly reduced microglial activation in mice treated with P2b and P2a, compared to PBS; and reduced infiltrative macrophages in mice treated with P2b compared to P2a and PBS. 

    Conclusion: These results show that redox-responsive nanotheranostic agents with a high number of ROS scavengers can mitigate RIBI-associated neuroinflammation and improve RIBI outcomes in brain tumor survivors.
  abstract_title_: 'Developing neuroprotective nanotheranostic agents for the image-guided treatment of radiotherapy-induced brain injury'
  email_address_: smaiti1@jhmi.edu
  institution_: 'Johns Hopkins University School of Medicine'
  presenting_author_: 'Saikat Maiti, Ph.D.'