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Detection of IL23p40 via Positron Emission Tomography Visualized Inflammatory Bowel Disease

Farzaneh Rezazadeh, Nicholas Ramos, Allen-Dexter Saliganan, Najeeb Al-Hallak, Kang Chen, Bashar Mohamad, Wendy N. Wiesend, View ORCID ProfileNerissa T. Viola
doi: https://doi.org/10.1101/2022.11.30.518419
Farzaneh Rezazadeh
1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201
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Nicholas Ramos
1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201
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Allen-Dexter Saliganan
1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201
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Najeeb Al-Hallak
1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201
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Kang Chen
2Departments of Obstetrics and Gynecology, Wayne State University, Detroit, MI
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Bashar Mohamad
3Department of Gastroenterology, Wayne State University, Detroit, MI
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Wendy N. Wiesend
4Department of Anatomic Pathology, Corewell Health William Beaumont University Hospital
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Nerissa T. Viola
1Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201
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  • ORCID record for Nerissa T. Viola
  • For correspondence: violan@karmanos.org
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Abstract

Background and aims Inflammatory bowel disease (IBD), which includes both Crohn’s Disease (CD) and ulcerative colitis (UC), is a relapsing inflammatory disease of the gastrointestinal (GI) tract. Long term chronic inflammatory conditions elevate patients’ risk for colorectal cancer (CRC). Currently, diagnosis requires endoscopy with biopsy. This procedure is invasive and requires bowel preparatory regimen, adding to patient burden. Interleukin 23 (IL23) plays a key role in inflammation especially in the pathogenesis of IBD and is an established therapeutic target. We propose that imaging of IL23 via immunopositron emission tomography (immunoPET) will potentially lead to a new non-invasive diagnostic approach.

Methods The aim of the present study is to investigate the potential of immunoPET to image inflammation in a chemically induced mouse model of colitis using dextran sodium sulfate (DSS) by targeting IL23 via its p40 subunit with a 89Zr-radiolabeled α-IL23p40 antibody.

Results High uptake of the IL23p40 immunoPET agent in mice were displayed in DSS-administered mice, which correlated with increased IL23p40 present in sera. Competitive binding studies confirmed the specificity of the radiotracer for IL23p40 in the GI tract.

Conclusion Taken together, these promising results set the stage for developing this radiotracer as an imaging biomarker for IBD diagnosis. Noninvasive imaging of IBD with IL23p40 immunoPET may help physicians in their treatment decisions for IBD management.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Grant support: The study was supported by NIH/NCI R37 CA220482 (NTV). The Microscopy, Imaging and Cytometry Resources Core (MICR) and Animal Modeling and Therapeutics Core, which provided technical assistance are supported, in part, by the NIH Cancer Center grant P30 CA022453 to the Karmanos Cancer Institute at Wayne State University, the Perinatology Research Branch of the National Institutes of Child Health and Development at Wayne State University.

  • Abbreviations used in this paper

    IBD
    inflammatory bowel disease
    CD
    Crohn’s Disease
    UC
    ulcerative colitis
    CRC
    colorectal cancer
    PET
    positron emission tomography
    IL
    interleukin
    GI
    gastrointestinal
    [18F]-FDG
    [18F]- Fluorodeoxyglucose
    DSS
    dextran sodium sulfate
    TNFα
    tumor necrosis factor alpha
    iTLC
    instant thin layer chromatography
    EDTA
    ethylenediaminetetraacetic acid
    VOI
    volumes-of-interest
  • Copyright 
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    Posted November 30, 2022.
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    Detection of IL23p40 via Positron Emission Tomography Visualized Inflammatory Bowel Disease
    Farzaneh Rezazadeh, Nicholas Ramos, Allen-Dexter Saliganan, Najeeb Al-Hallak, Kang Chen, Bashar Mohamad, Wendy N. Wiesend, Nerissa T. Viola
    bioRxiv 2022.11.30.518419; doi: https://doi.org/10.1101/2022.11.30.518419
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    Detection of IL23p40 via Positron Emission Tomography Visualized Inflammatory Bowel Disease
    Farzaneh Rezazadeh, Nicholas Ramos, Allen-Dexter Saliganan, Najeeb Al-Hallak, Kang Chen, Bashar Mohamad, Wendy N. Wiesend, Nerissa T. Viola
    bioRxiv 2022.11.30.518419; doi: https://doi.org/10.1101/2022.11.30.518419

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