Abstract
Single-photon emission computed tomography combined with micro-CT (SPECT/μCT) imaging using Nanobodies against complement receptor of the Ig superfamily (CRIg), found on tissue macrophages such as synovial macrophages, has promising potential to visualize joint inflammation in experimental arthritis. Here, we further addressed the specificity and assessed the potential for arthritis monitoring. Signals obtained with 99mTc-labelled NbV4m119 Nanobody were compared in joints of wild type (WT) versus CRIg−/− mice with collagen-induced arthritis (CIA) or K/BxN serum transfer-induced arthritis (STIA). In addition, SPECT/μCT imaging was used to investigate arthritis development in STIA and in CIA under dexamethasone treatment. 99mTc-NbV4m119 accumulated in inflamed joints of WT, but not CRIg−/− mice with CIA and STIA. Development and spontaneous recovery of symptoms in STIA was reflected in initially increased and subsequently reduced joint accumulation of 99mTc-NbV4m119. Dexamethasone treatment of CIA mice reduced 99mTc-NbV4m119 accumulation as compared to saline control in most joints except knees. SPECT/μCT imaging with 99mTc-NbV4m119 allows specific assessment of inflammation in different arthritis models and provides complementary information to clinical scoring for quantitatively and non-invasively monitoring the pathological process and the efficacy of arthritis treatment.
Highlights
Rheumatoid arthritis (RA) is a chronic destructive inflammatory disease of the joints, featuring a mixed mononuclear and granulocytic cellular infiltration in the inflamed joints[1]
In an approach of targeting markers expressed on macrophages for non-invasive inflammation tracking, we reported before that radiolabelled Nanobodies targeting the macrophage mannose receptor (NbMMR), initially described as effective probes for in vivo imaging of tumor-associated macrophages in hypoxic tumor areas[20,21], accumulate in joints of collagen-induced arthritis (CIA) mice[22]
As a first step in addressing the target specificity at the level of the cell-type expressing complement receptor of the Ig superfamily (CRIg) that is being targeted by the NbV4m119, CIA was induced in DBA/1 mice and immunofluorescence microscopy was performed on tissue sections of decalcified ankles exhibiting different arthritic scores
Summary
Rheumatoid arthritis (RA) is a chronic destructive inflammatory disease of the joints, featuring a mixed mononuclear and granulocytic cellular infiltration in the inflamed joints[1]. Most transgenic and knockout strains of mice are in a C57BL/6J background (H-2b), which is regarded to be relatively resistant to arthritis induction[5] In this context, it has been reported that C57BL/6J mice are susceptible to arthritis induced by chicken type II collagen with a modified immunization protocol. In an approach of targeting markers expressed on macrophages for non-invasive inflammation tracking, we reported before that radiolabelled Nanobodies targeting the macrophage mannose receptor (NbMMR), initially described as effective probes for in vivo imaging of tumor-associated macrophages in hypoxic tumor areas[20,21], accumulate in joints of CIA mice[22]. In line with a lower signal in non-arthritic joints, and a higher contrast for NbV4m119 as compared to NbMMR, accumulation of 99mTc-NbV4m119 in knees of mice developing CIA could even be detected before the onset of macroscopic clinical symptoms
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