# Fibrogenesis Targeted Manganese Based MRI Contrast Agent

> **NIH NIH R44** · REVEAL PHARMA · 2024 · $969,394

## Abstract

Nonalcoholic fatty liver disease (NAFLD) affects an estimated 20-30% of adults in the western world. Most
NAFLD is benign, but up to 30% of NAFLD patients will develop a progressive form of fatty liver termed
nonalcoholic steatohepatitis (NASH). NASH is the leading cause of severe liver disease, leading to >$175 billion
in healthcare costs over the next two decades in the US, and NASH prevalence is rising. Diagnosed early, NASH
may be reversed with lifestyle intervention. Unfortunately, the only way to distinguish NASH from benign fatty
liver is through invasive biopsy, which is impractical for repeated sampling to monitor disease progression or
treatment response. Thus there is a major unmet need for the noninvasive detection of NASH at an early stage.
A second major unmet need is the lack of a noninvasive method to assess treatment response in NASH.
 Histologic scoring of NASH is based on the presence of steatosis, hepatocellular ballooning, inflammation,
and fibrosis; however fibrosis is the only histologic feature that is linked to progression to cirrhosis, hepatocellular
carcinoma or liver failure. Technology to noninvasively image NASH disease activity which drives progression
of liver fibrosis could profoundly alter our ability to diagnose NASH and monitor treatment response. Serum
biomarker panels and ultrasound or magnetic resonance (MR) elastography methods can reasonably detect liver
fibrosis at very advanced stages (F4) but are ineffective at detecting earlier stages of fibrosis (F1, F2), and none
of these techniques have been shown to be effective in monitoring treatment response in clinical trials. These
unmet needs extend to other chronic liver diseases, e.g. primary sclerosing cholangitis, alcoholic steatohepatitis.
 We recently developed a class of gadolinium (Gd)-based MR imaging probes that are capable of quantifying
fibrogenesis – the disease activity process by which collagen is crosslinked and fibrosis occurs – through
molecular targeting of extracellular protein-bound aldehydes generated during collagen crosslinking. We have
shown in animal models that molecular MR of fibrogenesis has exquisite sensitivity for early fibrosis detection
and is also an early reporter of treatment response, noninvasively detecting positive tissue remodeling processes
prior to reduction in liver fibrosis. However, there is concern about the safety of Gd-based imaging probes due
to Gd retention and toxicity, thus limiting the commercial potential of Gd-based probes.
 Reveal Pharma has developed proprietary “RVP” manganese-chelate technology to replace the use of Gd in
MR agents. In this Fast Track application we will develop a Gd-free fibrogenesis-specific MR imaging probe. In
Phase I we will synthesize a library of probes and demonstrate fibrogenesis-specific imaging in a mouse model
of NASH. In Phase II, we will perform lead optimization; select a candidate “RVP-FI” for ultimate clinical
development; and validate both its safety and utility in ...

## Key facts

- **NIH application ID:** 10896265
- **Project number:** 5R44DK134295-03
- **Recipient organization:** REVEAL PHARMA
- **Principal Investigator:** Vera Hoffman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $969,394
- **Award type:** 5
- **Project period:** 2022-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896265

## Citation

> US National Institutes of Health, RePORTER application 10896265, Fibrogenesis Targeted Manganese Based MRI Contrast Agent (5R44DK134295-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10896265. Licensed CC0.

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