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Rheumatology (Oxford). 2018 Apr 1;57(4):737-747. doi: 10.1093/rheumatology/kex456.

Imaging fibroblast activation protein to monitor therapeutic effects of neutralizing interleukin-22 in collagen-induced arthritis.

Author information

1
Department of Radiology and Nuclear Medicine, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
2
Department of Experimental Rheumatology, Radboud University Medical Center Nijmegen, Nijmegen, The Netherlands.
3
Roche Pharmaceutical Research & Early Development, Innovation Center Basel, Basel, Switzerland.
4
Roche Pharmaceutical Research & Early Development, Innovation Center Zurich, Schlieren, Switzerland.
5
Inflammation & Immunology Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA.
6
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht.
7
Department of Targeted Therapeutics, MIRA Institute, University of Twente, Enschede, The Netherlands.
8
Department of Experimental Molecular Imaging, University Clinic & Helmholtz Institute for Biomedical Engineering, RWTH-Aachen University, Aachen, Germany.

Abstract

Objectives:

RA is a chronic autoimmune disease leading to progressive destruction of cartilage and bone. RA patients show elevated IL-22 levels and the amount of IL-22-producing Th cells positively correlates with the extent of erosive disease, suggesting a role for this cytokine in RA pathogenesis. The purpose of this study was to determine the feasibility of SPECT/CT imaging with 111In-labelled anti-fibroblast activation protein antibody (28H1) to monitor the therapeutic effect of neutralizing IL-22 in experimental arthritis.

Methods:

Mice (six mice/group) with CIA received anti-IL-22 or isotype control antibodies. To monitor therapeutic effects after treatment, SPECT/CT images were acquired 24 h after injection of 111In-28H1. Imaging results were compared with macroscopic, histologic and radiographic arthritis scores.

Results:

Neutralizing IL-22 before CIA onset effectively prevented arthritis development, reaching a disease incidence of only 50%, vs 100% in the control group. SPECT imaging showed significantly lower joint tracer uptake in mice treated early with anti-IL-22 antibodies compared with the control-treated group. Reduction of disease activity in those mice was confirmed by macroscopic, histological and radiographic pathology scores. However, when treatment was initiated in a later phase of CIA, progression of joint pathology could not be prevented.

Conclusion:

These findings suggest that IL-22 plays an important role in CIA development, and neutralizing this cytokine seems an attractive new strategy in RA treatment. Most importantly, SPECT/CT imaging with 111In-28H1 can be used to specifically monitor therapy responses, and is potentially more sensitive in disease monitoring than the gold standard method of macroscopic arthritis scoring.

PMID:
29361119
DOI:
10.1093/rheumatology/kex456
[Indexed for MEDLINE]

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