# MRI biosensors and complementary drug nanocarriers for effective image-guided drug delivery and early tumor response assessment of pediatric medulloblastomas

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2020 · $204,194

## Abstract

Chemotherapy is a major component of all pediatric medulloblastoma treatment plans. However, reports
suggest that less than 1% of drugs administered intravenously reach brain tumors. One of the challenges of
delivering drugs to brain tumors is the blood brain barrier (BBB), which restricts drug penetration into brain
tumors. Targeted drug delivery systems and targeted interventional procedures capable of traversing the BBB
could improve drug delivery into brain tumors. These targeted drug delivery systems will tremendously benefit
from noninvasive imaging approaches to monitor the drug delivery process. Also critical is the need for
noninvasive prognostic imaging markers, capable of predicting early tumor response or tumor resistance to
therapy, following drug delivery. These imaging tools will be essential in validating the efficiency of the drug
delivery process and will enable more effective patient management, by permitting the rapid selection of the
most effective treatment option and dose escalation scale. These efforts will bring personalized therapeutic
regimens one step closer to realization. The overall objective of this project is to develop molecular magnetic
resonance imaging (MRI) biosensors capable of directly and noninvasively imaging drug delivery across the BBB
and into brain tumors, and also capable of imaging early molecular changes associated with tumor response or
tumor resistance to therapy. Chemical exchange saturation transfer MRI (CEST MRI), is a relatively new MRI
technique which shows promise for imaging organic molecules by saturating specific exchangeable protons
(such as amine, amide and hydroxyl protons) on the molecules of interest, with defined radiofrequency pulses.
Although, CEST MRI is based on a magnetic resonance spectroscopic (MRS) technique, it is several orders of
magnitude more sensitive than MRS. We postulate that the labile protons of some DNA alkylating agents
generate a pH-dependent CEST MRI contrast signal that can be used to monitor their delivery to brain tumors,
and also to report on early molecular tumor changes in response to therapy. This project will be achieved through
two specific aims. In aim 1, we will screen six DNA alkylating agents and evaluate each drug’s potential to act
as a CEST MRI biosensor. From this aim we will obtain a signature CEST MRI profile for each drug, which will
enable us to detect the drug in tumors after drug delivery. In aims 2, we will evaluate the feasibility of using the
signature CEST MRI contrast profiles of the respective biosensors to detect drug delivery during a targeted
interventional procedure and also from targeted drug nanocarriers. We will also evaluate the feasibility of using
the pH-dependent CEST signal of the biosensors to image early tumor response or tumor resistance to therapy,
in vivo. All CEST MRI results will be validated with bioluminescence imaging, immunohistochemistry using drug-
specific antibodies, histology, multi-parametric MRI and p...

## Key facts

- **NIH application ID:** 10005400
- **Project number:** 5R21HD097357-02
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ethel Joso Ngen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,194
- **Award type:** 5
- **Project period:** 2019-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10005400

## Citation

> US National Institutes of Health, RePORTER application 10005400, MRI biosensors and complementary drug nanocarriers for effective image-guided drug delivery and early tumor response assessment of pediatric medulloblastomas (5R21HD097357-02). Retrieved via AI Analytics 2026-07-05 from https://api.ai-analytics.org/grant/nih/10005400. Licensed CC0.

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