# Manganese Based MRI Contrast Agent

> **NIH NIH R44** · REVEAL PHARMA · 2024 · $2,025,000

## Abstract

Gadolinium (Gd)-based MRI contrast agents (GBCAs) are used in clinical magnetic resonance imaging (MRI)
for cancer detection and staging, particularly of primary and metastatic brain cancers. However, there are
concerns about the potential long-term toxicity of GBCAs. GBCAs cause nephrogenic systemic fibrosis (NSF),
a devastating disorder that affects patients with kidney disease. FDA imposed a “black box” warning against
GBCA use in this population. This has a significant medical impact: 16% of US adults suffer from moderate or
severe chronic kidney disease (CKD), and this patient population is disproportionately afflicted with comorbidities
like cancer (where many chemotherapies are nephrotoxic). There is no alternative imaging for these patients.
Contrast enhanced CT can cause acute and irreversible kidney injury and is also contraindicated. All GBCAs
cause accumulation of Gd in the brain and bone, even in patients with normal kidney function. Gd is highly toxic
in its free form, and little is known about the toxicological implications of deposited Gd: concern is rising among
physicians, patients, and regulatory agencies. In 2017 the FDA announced a new class warning for all GBCAs.
The European Medicines Agency suspended the marketing authorizations for the 4 GBCAs that are associated
with the highest risk of Gd deposition, and arguably may have removed all GBCAs had there been a safe, Gd-
free alternative. Accumulation of Gd is particularly worrisome for cancer survivors and those at high risk for
cancer, e.g. BRCA positive women. They require regular GBCA-enhanced MRIs for surveillance or screening,
and may have dozens of MRIs through life. Avoiding GBCAs forces physicians to make key patient management
decisions with limited imaging information, while continued use may put these vulnerable patients at risk.
 Reveal Pharmaceuticals is developing the gadolinium-free MRI contrast agent, RVP-001, invented at
Massachusetts General Hospital. RVP-001 provides equivalent image contrast to commercial GBCAs in different
animal models. Manganese (Mn) injected as RVP-001 is more efficiently eliminated than Gd from an equal dose
of Gd-DOTA, which is considered the best in class GBCA for safety with respect to stability. Nonclinical studies
established a very high safety margin for RVP-001. A Phase 1 study to assess safety, tolerability, and
pharmacokinetics in healthy subjects demonstrated that RVP-001 is safe and well tolerated up to doses higher
than the anticipated clinical dose. This grant will support first in human MR imaging studies. We will perform a
dose range finding study in patients with GBCA-enhancing central nervous system lesions, e.g. brain cancers,
to assess imaging efficacy, pharmacodynamics, and safety. We will assess the degree of RVP-001 lesion
enhancement compared to unenhanced MRI and compared to the patient’s GBCA enhanced MRI. The goal of
the study is to establish an effective dose for further clinical development and approval.
...

## Key facts

- **NIH application ID:** 10861085
- **Project number:** 5R44CA261240-05
- **Recipient organization:** REVEAL PHARMA
- **Principal Investigator:** Vera Hoffman
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $2,025,000
- **Award type:** 5
- **Project period:** 2023-06-05 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10861085

## Citation

> US National Institutes of Health, RePORTER application 10861085, Manganese Based MRI Contrast Agent (5R44CA261240-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10861085. Licensed CC0.

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