# MR Signal Amplification for Receptor Imaging

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $407,779

## Abstract

The MRamp strategy was initially designed with the goal of improving the molecular sensitivity of MR
imaging by modulating the MR signal output on two levels simultaneously: 1) target specificity: a pair of
receptor-targeted enzymes co-localize in the specific tissue compartment and due to enzymatic activity
complementation, enable rapid modification of low molecular weight paramagnetic substrates which results in
their local retention at the reaction site; and 2) sensitivity: local retention gives rise to an amplified MR signal
generated by both high local concentration density and increased relaxivity of the paramagnetic products of the
enzymatic reaction. We have marked major milestones in bringing the MRamp technique closer to clinical
translation including: 1) demonstration of MRI of endogenous myeloperoxidase activity in human pathology
and in various disease models; 2) successful imaging of receptor expression in cancer models. MRamp is one
of the few existing techniques enabling the detection of the co-expression of two protein markers (receptors).
We recently explored co-expression imaging feasibility with µPET-CT in addition to MRI. By implementing an
expanded multi-modality imaging approach (BLI, MRI and µPET-CT), we previously identified osteolytic and
non-osteolytic triple-negative breast cancer (TNBC) phenotypes and characterized them using the analysis of
key gene transcripts. The new phase of research proposed here, will include the optimization of a dual receptor
imaging strategy and its application to in vivo imaging of two critically important biomarkers of TNBC, i.e.
overexpressed EGFR and PD-L1. The ability to image the co-expression of these critical markers in TNBC
tumors is expected to provide a new, highly quantifiable and easily interpretable diagnostic imaging method
that can be used to (1) detect metastatic spread, (2) select patients for targeted therapies and (3) monitor
therapeutic response or resistance over the course of treatment. In addition to simplifying the monitoring of
patients undergoing existing cancer treatments, this new methodology could speed testing of investigational
new drugs in clinical trials thus expediting approval of promising new TNBC therapies. Our initial goal will be to
screen novel chimeric small molecule catalyst-substrates, to select candidates for highest MR and PET signal
amplification using our enzyme dependent imaging system. We have previously published on inroads made in
our design of MR detectable paramagnetic Mn(II)-based superoxide dismutase mimetics and will further
harness their power as tools for miniaturizing our MRamp system. Such miniaturization may prove essential for
the ability to tag and track extracellular vesicles (EV) in vivo which are now believed to be a key element in the
metastatic spread of cancers such as TNBC. Therefore, a second major goal of this proposal will be to image
endogenously occurring EVs using our dual receptor, high sensitivity enzyme complemen...

## Key facts

- **NIH application ID:** 10001065
- **Project number:** 5R01EB000858-15
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Alexei A. Bogdanov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $407,779
- **Award type:** 5
- **Project period:** 2003-04-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001065

## Citation

> US National Institutes of Health, RePORTER application 10001065, MR Signal Amplification for Receptor Imaging (5R01EB000858-15). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001065. Licensed CC0.

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