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

Submission information
Submission Number: 39
Submission ID: 148272
Submission UUID: 9a42c1ad-f8cf-4e3f-acc6-deaa5acdf05a

Created: Wed, 08/06/2025 - 22:33
Completed: Wed, 08/06/2025 - 23:01
Changed: Wed, 08/06/2025 - 23:01

Remote IP address: 10.208.28.64
Submitted by: Anonymous
Language: English

Is draft: No
Abstract Title: Developing neuroprotective nanotheranostic agents for the image-guided treatment of radiotherapy-induced brain injury
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:
Authors:
  1. First Name: Saikat
    Last Name: Maiti
    Degree(s): Ph.D.
    Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
  2. First Name: Maya
    Last Name: Teitz
    Degree(s): B.Sc.
    Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
  3. First Name: Esteban
    Last Name: Velarde
    Degree(s): B.Sc.
    Organization: Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231
  4. First Name: Xiaoju
    Last Name: Yang
    Degree(s): Ph.D.
    Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
  5. First Name: Shana
    Last Name: Lee
    Degree(s): B.SC.
    Organization: Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205
  6. First Name: Kristen
    Last Name: Lecksell
    Degree(s): B.Sc.
    Organization: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287
  7. First Name: Barbara
    Middle Initial: J.
    Last Name: Smith
    Degree(s): B.Sc.
    Organization: Department of Cell Biology, Baltimore, MD 21205
  8. First Name: Anupama
    Last Name: Kumari
    Degree(s): Ph.D.
    Organization: Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287
  9. First Name: Adnan
    Last Name: Bibic
    Degree(s): Ph.D.
    Organization: F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205
  10. First Name: Ethel
    Middle Initial: J.
    Last Name: Ngen
    Degree(s): Ph.D.
    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
Presenting Author: Saikat Maiti, Ph.D.
Institution: Johns Hopkins University School of Medicine
Email Address: smaiti1@jhmi.edu