# Sensitivity enhanced MRI imaging of receptor binding in breast cancer

> **NIH NIH R21** · HUGO W. MOSER RES INST KENNEDY KRIEGER · 2020 · $202,000

## Abstract

Cancer remains one of the leading causes of death in the industrialized world. In recent years, there has been
a resurgence of interest in tumor lactate metabolism since lactate has been associated with metastases and
poor prognosis in cancer patients. Recent discoveries have identified that the cell surface lactate receptor
HCA1 is associated with tumorigenesis and metastasis and thus an attractive imaging target and possible
therapeutic target. However, because lactate exhibits low affinity and a fast turnover rate, current in vivo
molecular imaging techniques are not well suited to image these types of targets. We have developed a novel
MRI based approach for detecting the low affinity binding of natural (no chemical modification) substrates to
molecular targets and a unique molecular pump scheme that enhances the sensitivity two to three orders of
magnitude thus making this technology applicable for in vivo studies. Importantly, this method can be
implemented on standard MRI hardware and thus rapidly translated to the clinic. We propose developing,
optimizing, and validating this approach for imaging the binding of lactate to HCA1 receptors in breast cancer.
 In AIM 1, we will validate the specificity of detecting lactate-HCA1 binding in vitro using (i) perfused
breast cancer cells that express different levels of the HCA1 receptor, and (ii) MRI pulse sequence
optimization. In AIM 2, we will validate the specific binding of lactate to breast cancer cells in vivo. We will
further probe lactate binding using the infusion of L-lactate or D-glucose (metabolized to lactate), both FDA
approved for iv use in humans.
 These aims are expected to result in a MRI method for imaging the binding of low-affinity ligands to
a cell target. Due to the nature of the labelling approaches, these MRI methods will be highly tunable to a
broad range of other substrates-target pairs.

## Key facts

- **NIH application ID:** 9899981
- **Project number:** 5R21EB025295-03
- **Recipient organization:** HUGO W. MOSER RES INST KENNEDY KRIEGER
- **Principal Investigator:** Nirbhay Narayan Yadav
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $202,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899981

## Citation

> US National Institutes of Health, RePORTER application 9899981, Sensitivity enhanced MRI imaging of receptor binding in breast cancer (5R21EB025295-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9899981. Licensed CC0.

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