Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.
Bottom Line: Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis.A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes.In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers.
Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ₃ integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.
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Mentions: F4/80, a member of the epidermal growth factor transmembrane 7 family, is expressed on a variety of macrophage subsets. Macrophages that accumulate in inflamed joints express F4/80. In a mouse model, imaging with NIR-labeled antibodies targeting F4/80 visualized macrophage accumulation in arthritic joints, with some background in healthy paws . The MMR is a 175-kDa C-type lectin expressed predominantly by mature macrophages and certain endothelial and dendritic cells. It is detected in spleen, liver, and lymph nodes and its primary functions are endocytic clearance of certain glycoproteins and phagocytosis of unopsonized microorganisms . Our research group recently reported the successful use of radiolabeled nanobodies targeting MMR for in vivo SPECT/CT imaging of mice with CIA (Figure 4) . We were able to visualize CD11b+F4/80+ macrophages in the inflamed joints of these mice, thereby providing a means to quantify the inflammation in an objective manner and obtaining more knowledge on the pathogenesis of arthritis, since MMR had previously not been shown to be expressed in the rheumatic synovium .