Assessment of rat antigen-induced arthritis and its suppression during glucocorticoid therapy by use of hemicyanine dye probes with different molecular weight in near-infrared fluorescence optical imaging

Abstract

Purpose: Arthritic joints are ideal disease entities to be assessed via optical imaging. Here, we investigated the selective accumulation behavior of two differently sized hemicyanine optical probes in arthritic joints and its modification during glucocorticoid therapy in the course of inflammation.

Materials and methods: The well-standardized preclinical antigen-induced arthritis (AIA) model in rats was used. The animals were divided into 3 groups: arthritic, arthritic and dexamethasone-treated, and immunized only. After intravenous coinjection of DY-752 (size, 800 Da) and DY-682-(rat) IgG (size, 150 kDa) probes, spectrally unmixed near-infrared fluorescence images were acquired and analyzed semiquantitatively. Probe organ distribution, joint swelling, blood cell counts, joint vessel density, and histological scoring of arthritis were determined.

Results: The local joint accumulation kinetics of the DY-752 probe differed from the DY-682-IgG one. In the course of AIA, probe signaling in arthritic joints was similar between each other. Joint swelling and histological scoring were in accordance with signaling. Dexamethasone treatment of rats with AIA significantly reduced both the near-infrared fluorescence signals and severity of arthritis but did not change the joint vascular density or the uptake of the probes by phagocytes. A differential biodistribution of both probes was encountered, but such an accumulation was prevented by dexamethasone treatment.

Conclusions: Near-infrared fluorescence signaling in the course of AIA closely reflects the pathophysiological events of the arthritic joint and the effects of therapy independently of the molecular size of the probe. The results show the suitability of our hemicyanine probes for imaging of arthritis.