In Vivo PET Imaging of the Activated Immune Environment in a Small Animal Model of Inflammatory Arthritis

Mol Imaging. 2017 Jan 1:16:1536012117712638. doi: 10.1177/1536012117712638.

Abstract

Background: Evolving immune-mediated therapeutic strategies for rheumatoid arthritis (RA) may benefit from an improved understanding of the complex role that T-cell activation plays in RA. This study assessed the potential of fluorine-18-labeled 9-β-d-arabinofuranosylguanine ([18F]F-AraG) positron emission tomography (PET) imaging to report immune activation in vivo in an adjuvant-induced arthritis (AIA) small animal model.

Methods: Using positron emission tomography-computed tomography imaging, uptake of [18F]F-AraG in the paws of mice affected by arthritis at 6 (acute) and 20 (chronic) days following AIA induction in a single paw was assessed and compared to uptake in contralateral control paws. Fractions of T cells and B cells demonstrating markers of activation at the 2 time points were determined by flow cytometry.

Results: Differential uptake of [18F]F-AraG was demonstrated on imaging of the affected joint when compared to control at both acute and chronic time points with corresponding changes in markers of T-cell activation observed on flow cytometry.

Conclusion: [18F]F-AraG may serve as an imaging biomarker of T-cell activation in inflammatory arthritis. Further development of this technique is warranted and could offer a tool to explore the temporal link between activated T cells and RA as well as to monitor immune-mediated therapies for RA in clinical trials.

Keywords: animal models of disease; molecular imaging of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis / immunology*
  • Arthritis / metabolism*
  • B-Lymphocytes / metabolism
  • Disease Models, Animal
  • Flow Cytometry
  • Mice
  • Mice, Inbred BALB C
  • Molecular Imaging / methods
  • Positron-Emission Tomography / methods*
  • T-Lymphocytes / metabolism