# CEST MRI Agents for Receptor Imaging

> **NIH NIH P41** · JOHNS HOPKINS UNIVERSITY · 2020 · $260,599

## Abstract

SUMMARY for TR&D 4
The overarching goal of TR&D 4 is to introduce concepts of precision medicine to chemical exchange saturation
transfer (CEST) magnetic resonance imaging (MRI). CEST MRI amplifies signal from macromolecular species
that contain protons in exchange with water. Currently CEST leverages the suitable chemical shift frequencies
and exchange rates of amide or hydroxyl protons. One may use CEST for detection of proteins that naturally
contain many such functionalities or for exogenously administered, artificial agents, such as the lysine-rich
reporter from TR&D 2. As such CEST is not an inherently targeted (to phenotypically expressed proteins) or
precision method. TR&D 4 of the BTRC will generate and disseminate precision CEST agents. We will develop
non-metallic, targeted MR agents for receptor imaging with a focus on polymeric species to ensure adequate
signal. Currently, about one third of all MRI scans rely on administration of non-specific relaxation-based
gadolinium contrast agents to aid in the clinical differentiation of healthy and diseased tissues, however in view
of recent concerns about accumulation of gadolinium in brain and bone, there is an increasing demand for non-
metallic agents. CEST MRI allows the imaging of low-concentration compounds with the molar sensitivity of MRI
and also has the advantages that CEST agents can be designed to be biodegradable. We will synthesize
translatable CEST MRI agents for receptor-based imaging together with acquisition and analysis approaches
that are optimized for the properties of each individual agent. To accomplish this, in Aim 1, we will conjugate a
PSMA targeting ligand to highly sensitive CEST polymers, including dextran polymers as biocompatible agents
and salicylic acid polymers as higher sensitivity polymers. We will then optimize pulse sequences for detecting
the polymeric agents in terms of exchange rate and chemical shift (Aim 2). The pulse sequences developed in
Aim 2 will also be applied to TR&D 2. In Aim 3 we will further proceed to investigate two other clinically relevant
receptors, carbonic anhydrase IX (CA-IX), the expression of which has implications for the tumor
microenvironment, and Axl tyrosine kinase. CA-IX is an antigen expressed on clear cell renal cell carcinoma
(ccRCC), and could provide valuable information for radical nephrectomy and renal cancer surveillance. In Aim
4, we will generate cGMP-grade material of the most promising item in the Center for Translational Molecular
Imaging on the pathway to human use. For this step, the agents generated will be tested in preliminary toxicity
studies will be performed prior to GLP toxicity testing.

## Key facts

- **NIH application ID:** 9984358
- **Project number:** 5P41EB024495-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** MICHAEL T MCMAHON
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $260,599
- **Award type:** 5
- **Project period:** 2017-09-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984358

## Citation

> US National Institutes of Health, RePORTER application 9984358, CEST MRI Agents for Receptor Imaging (5P41EB024495-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984358. Licensed CC0.

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