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Imaging kidney inflammation using an oxidatively activated MRI probe
Ivy A Rosales1, Iris Yuwen Zhou2, Ilknur Ay2
1Department of Pathology, Immunopathology Research Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Kidney International
|June 20, 2024
Summary
New MRI contrast agent Fe-PyC3A detects kidney inflammation by identifying an oxidizing microenvironment. This imaging tool shows promise for diagnosing inflammatory kidney diseases, potentially reducing the need for biopsies.
Area of Science:
- Biomedical Imaging
- Renal Medicine
- Immunology
Background:
- Kidney inflammation diagnosis often relies on invasive biopsies or biochemical tests.
- Inflammatory kidney diseases create an oxidizing microenvironment due to myeloid immune cell infiltration.
- Novel imaging techniques are needed to non-invasively assess kidney inflammation.
Purpose of the Study:
- To evaluate magnetic resonance imaging (MRI) with a redox-active iron complex (Fe-PyC3A) as a marker for kidney inflammation.
- To assess the specificity of Fe-PyC3A for the oxidizing conditions present in inflamed kidneys.
- To preliminarily examine the safety of Fe-PyC3A.
Main Methods:
- Utilized mouse models of unilateral ischemia-reperfusion injury (IRI) and lupus nephritis (MRL-lpr mice).
- Administered Fe-PyC3A and gadoterate meglumine (control) for MRI.
- Compared MRI signal enhancement in inflamed vs. healthy kidneys and in wild-type vs. knockout mice (gp91phox-/-).
Main Results:
- Fe-PyC3A showed significantly greater MRI signal enhancement in IRI kidneys compared to contralateral kidneys in wild-type mice.
- This enhancement was absent in NOX2-deficient mice, indicating specificity to myeloid oxidative activity.
- Fe-PyC3A demonstrated greater kidney enhancement in MRL-lpr mice compared to controls.
- Gadoterate meglumine did not show differential enhancement between inflamed and healthy kidneys.
Conclusions:
- MRI with Fe-PyC3A is specific to the oxidizing kidney environment driven by myeloid immune cells.
- Fe-PyC3A shows potential as a non-invasive imaging biomarker for kidney inflammation.
- Further evaluation of Fe-PyC3A for clinical imaging of inflammatory kidney diseases is warranted.
