# Image-guided combination therapies for radiotherapy-induced neurocognitive impairment in pediatric brain tumor survivors

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $584,003

## Abstract

Approximately 90% of pediatric central nervous system tumor (CNST) survivors, treated with radiotherapy,
experience radiotherapy-induced brain injury (RIBI) and neurocognitive decline later in life. This is a progressive
treatment-related side effect, which impacts the quality of life of pediatric CNST survivors. Since more pediatric
patients are surviving cancer, there is a growing need for RIBI prophylactic and therapeutic strategies. Chronic
oxidative stress and neuroinflammation are key contributors to RIBI. Thus, neuroprotective strategies to reduce
oxidative stress and neuroinflammation are being explored. Neuroengineering strategies using regenerative
stem cells to repair RIBI are also being explored. However, prolonging the survival of transplanted stem cells at
injury sites is a challenge, partly due to chronic oxidative stress and neuroinflammation. Accordingly, strategies
to improve transplanted stem cell survival are on the horizon. For these strategies to be effective, drug delivery
systems capable of effectively delivering neuroprotective drugs to brain injuries are greatly needed. Also critical
for clinical translation efforts are methods to noninvasively image drug delivery and tissue responses to therapy.
Nanotechnology in combination with image-guided neuro-interventional procedures are promising for drug
delivery. In addition, diamagnetic chemical exchange saturation transfer magnetic resonance imaging (CEST
MRI) is a promising MRI technique that can be used to noninvasively and directly image organic drugs. Although,
CEST MRI is based on a magnetic resonance spectroscopic (MRS) technique, it is more sensitive (~1000 times)
than MRS. Furthermore, given the inherent correlation between CEST MRI signals, pH, and oxidative stress, it
can also be used to image changes in tissue oxidative stress, in response to effective drug delivery. We propose
to develop CEST MRI theranostic biosensors and complementary CEST MRI nanotheranostic agents for image-
guided combination therapy of RIBI. In Aim 1, neuroprotective drugs will be screened by CEST MRI, and each
drug’s potential to serve as a pH-dependent CEST MRI theranostic biosensor will be evaluated in our preclinical
RIBI model. The feasibility of imaging changes in tissue oxidative stress in vivo with the CEST MRI theranostic
agents will also be evaluated. In Aim 2, we will develop oxidative stress-activable CEST MRI nanotheranostic
biosensors and evaluate each agent’s potential to sustainably reduce oxidative stress and neuroinflammation in
our RIBI model. In Aim 3, we will evaluate the feasibility of improving transplanted stem cell survival and
neurorepair in our RIBI model, by sustainably reducing oxidative stress and neuroinflammation. Stem cell
survival will be imaged with our stem cell tracking MRI biosensor, capable of noninvasively imaging stem cell
delivery, migration and survival. All results will be validated with multi-parametric MRI; PET imaging of
neuroinflammation, usin...

## Key facts

- **NIH application ID:** 10449372
- **Project number:** 5R01CA262887-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ethel Joso Ngen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $584,003
- **Award type:** 5
- **Project period:** 2021-07-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449372

## Citation

> US National Institutes of Health, RePORTER application 10449372, Image-guided combination therapies for radiotherapy-induced neurocognitive impairment in pediatric brain tumor survivors (5R01CA262887-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10449372. Licensed CC0.

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