Immuno-PET of innate immune markers CD11b and IL-1b detects inflammation in murine colitis

Nicole Dmochowska, William Tieu, Marianne D. Keller, Hannah R. Wardill, Chris Mavrangelos, Melissa A. Campaniello, Prab Takhar, Patrick Hughes

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate–treated colitic mice. PET of 89Zr-lα-IL-1β, 89Zr-α-CD11b, and 18F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89Zr-α-IL-1β and 89Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18F-FDG, and all PET tracers were more sensitive than MRI. Although 18F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89Zr-α-IL-1β, no correlation was observed for 89Zr-α-CD11b or MRI. 89Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89Zr-α-IL-1β providing a more tissue-specific signal than 89Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD.

LanguageEnglish
Pages858-863
Number of pages6
JournalJournal of Nuclear Medicine
Volume60
Issue number6
DOIs
Publication statusPublished - 1 Jun 2019

Keywords

  • Colitis
  • Immuno-PET
  • Inflammatory bowel disease
  • Innate immune system

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{3aa6b58c4ab043b9bdc10dfe59eda806,
title = "Immuno-PET of innate immune markers CD11b and IL-1b detects inflammation in murine colitis",
abstract = "Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate–treated colitic mice. PET of 89Zr-lα-IL-1β, 89Zr-α-CD11b, and 18F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89Zr-α-IL-1β and 89Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18F-FDG, and all PET tracers were more sensitive than MRI. Although 18F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89Zr-α-IL-1β, no correlation was observed for 89Zr-α-CD11b or MRI. 89Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89Zr-α-IL-1β providing a more tissue-specific signal than 89Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD.",
keywords = "Colitis, Immuno-PET, Inflammatory bowel disease, Innate immune system",
author = "Nicole Dmochowska and William Tieu and Keller, {Marianne D.} and Wardill, {Hannah R.} and Chris Mavrangelos and Campaniello, {Melissa A.} and Prab Takhar and Patrick Hughes",
year = "2019",
month = "6",
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doi = "10.2967/jnumed.118.219287",
language = "English",
volume = "60",
pages = "858--863",
journal = "Journal of Nuclear Medicine",
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Immuno-PET of innate immune markers CD11b and IL-1b detects inflammation in murine colitis. / Dmochowska, Nicole; Tieu, William; Keller, Marianne D.; Wardill, Hannah R.; Mavrangelos, Chris; Campaniello, Melissa A.; Takhar, Prab; Hughes, Patrick.

In: Journal of Nuclear Medicine, Vol. 60, No. 6, 01.06.2019, p. 858-863.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Immuno-PET of innate immune markers CD11b and IL-1b detects inflammation in murine colitis

AU - Dmochowska, Nicole

AU - Tieu, William

AU - Keller, Marianne D.

AU - Wardill, Hannah R.

AU - Mavrangelos, Chris

AU - Campaniello, Melissa A.

AU - Takhar, Prab

AU - Hughes, Patrick

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate–treated colitic mice. PET of 89Zr-lα-IL-1β, 89Zr-α-CD11b, and 18F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89Zr-α-IL-1β and 89Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18F-FDG, and all PET tracers were more sensitive than MRI. Although 18F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89Zr-α-IL-1β, no correlation was observed for 89Zr-α-CD11b or MRI. 89Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89Zr-α-IL-1β providing a more tissue-specific signal than 89Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD.

AB - Inflammatory bowel disease (IBD) is a chronic relapsing and remitting inflammatory disease of the gastrointestinal tract. The diagnosis and monitoring of IBD are reliant on endoscopy, which is invasive and does not provide information on specific mediators. Symptom flare in IBD is associated with increased activation of innate immune pathways. Immuno-PET approaches have previously demonstrated the ability to detect colitis; however, a direct comparison of antibodies targeted to innate immune mediators and cells has not been done. We aimed to compare immuno-PET of antibodies to IL-1β and CD11b against standard 18F-FDG and MRI approaches to detect colonic inflammation. Methods: Colonic concentrations of IL-1β and myeloperoxidase were determined by ELISA, and colonic infiltration by CD11b-positive CD3-negative innate immune cells was determined by flow cytometry and compared between healthy and dextran sodium sulphate–treated colitic mice. PET of 89Zr-lα-IL-1β, 89Zr-α-CD11b, and 18F-FDG was compared by volume-of-interest analysis and with MRI by region-of-interest analysis. Imaging results were confirmed by ex vivo biodistribution analysis. Results: Colonic inflammation was associated with impaired colonic epithelial barrier permeability, increased colonic IL-1β and myeloperoxidase concentrations, and increased CD11b-positive CD3-negative innate immune cell infiltration into the colon. 89Zr-α-IL-1β and 89Zr-α-CD11b immuno-PET detected colonic inflammation, as did 18F-FDG, and all PET tracers were more sensitive than MRI. Although 18F-FDG volumes of interest correlated with colitis severity and a strong trend was observed with 89Zr-α-IL-1β, no correlation was observed for 89Zr-α-CD11b or MRI. 89Zr-α-IL-1β was distributed mainly to the gastrointestinal tract, whereas 89Zr-α-CD11b was distributed to more tissue types. Conclusion: Immuno-PET using antibodies directed to innate immune markers detected colonic inflammation, with 89Zr-α-IL-1β providing a more tissue-specific signal than 89Zr-α-CD11b. Development of these technologies for human subjects will potentially provide a less invasive approach than endoscopy for diagnosing and monitoring IBD.

KW - Colitis

KW - Immuno-PET

KW - Inflammatory bowel disease

KW - Innate immune system

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U2 - 10.2967/jnumed.118.219287

DO - 10.2967/jnumed.118.219287

M3 - Article

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JO - Journal of Nuclear Medicine

T2 - Journal of Nuclear Medicine

JF - Journal of Nuclear Medicine

SN - 0161-5505

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