# Noninvasive Nephritis Imaging

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $250,827

## Abstract

Project Summary/Abstract.
Inflammation plays a key pathogenic role in numerous kidney disease states. Accordingly, procedures to
diagnose, map, and longitudinally monitor kidney inflammation can greatly enhance our ability to identify and
treat patients suffering from kidney injury related to drug toxicity, ischemia, infection, autoimmune diseases, and
allograft dysfunction. Unfortunately, definitive diagnosis of kidney inflammation requires biopsy, which is
invasive, costly, poses substantial bleeding risk, and samples only a small segment of the kidney. Repeat biopsy
is impractical for longitudinal patient monitoring. Furthermore, many patients requiring biopsy have
contraindications including obesity, anticoagulation, severe hypertension, or single kidney.
 There is an urgent unmet need to noninvasively detect, map, quantify, and monitor inflammation in numerous
kidney disease states. Currently available imaging technologies which could potentially identify kidney
inflammation, such as [18F]fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) have important
limitations, lacking sufficient spatial resolution for disease mapping, exposing patients to ionizing radiation, and
the fact that FDG is both renally excreted and partially reabsorbed in proximal tubules blunts visualization of
parenchymal inflammatory infiltrates. Experimental ultrasmall paramagnetic iron-oxide nanoparticles (USPIONs)
targeted to phagocytic cells have been used to image kidney inflammation in clinical trials, but this approach is
limited by slow USPION pharmacokinetics, requiring several days between injection and imaging readout.
 An ideal technology for molecular imaging of kidney inflammation should generate no background signal in
the kidney, generate positive signal enhancement in the presence of inflammation, and yield an inflammation-
specific imaging readout within minutes of injection. We posit that we can satisfy these technologic criteria
using new class of reactive oxygen species (ROS) responsive MR imaging probe recently invented by
our lab. Elevated extracellular ROS concentrations are a hallmark feature of inflamed tissue, as granulocytic
cells of the innate immune system undergo respiratory burst resulting in an aberrant oxidizing tissue
microenvironment. Our ROS-specific contrast agent, Fe-PyC3A, is a low molecular weight iron complex that
instantaneously switches between an MR silent and MR visible states in the presence ROS.
 The goals of this R21 are to advance Fe-PyC3A as tool for imaging kidney inflammation by demonstrating
proof of concept in murine models of ischemia- and immune-related kidney diseases, optimizing the dose for
kidney MR imaging, and demonstrating safety for kidney imaging applications. This proposal is written in
response to PAR-20-140 “Catalytic Tool and Technology Development in Kidney, Urologic, and Hemotologic
Diseases,” and specifically addresses calls for “innovative new radiologic methods and novel imaging probes.”...

## Key facts

- **NIH application ID:** 10490328
- **Project number:** 5R21DK130004-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Eric Michael Gale
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $250,827
- **Award type:** 5
- **Project period:** 2021-09-21 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490328

## Citation

> US National Institutes of Health, RePORTER application 10490328, Noninvasive Nephritis Imaging (5R21DK130004-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10490328. Licensed CC0.

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