Abstract
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.
Highlights
Anatomical imaging techniques have long been used to diagnose and monitor rheumatoid arthritis (RA)
Fluorescence imaging holds more promise for clinical applications, especially since the development of NIR probes that allow deeper penetration into tissues and less background interference. Nuclear imaging techniques, such as scintigraphy, Positron emission tomography (PET), and Singlephoton emission computed tomography (SPECT), use markers that are labeled with radioisotopes
PET imaging with 64Cu-labeled RGD allowed detection of changes in osteoclast numbers in mouse models for osteopetrosis or osteoporosis [70], suggesting that 64Cu-RGD may be suitable for imaging of osteoclast changes in RA
Summary
Anatomical imaging techniques have long been used to diagnose and monitor rheumatoid arthritis (RA). Fluorescence imaging holds more promise for clinical applications, especially since the development of NIR probes that allow deeper penetration into tissues and less background interference Nuclear imaging techniques, such as scintigraphy, PET, and SPECT, use markers that are labeled with radioisotopes. SPECT imaging with 99mtechnetium-methylene diphosphonate (99mTc-MDP) is clinically approved for the assessment of bone damage in RA and is used to monitor patients with active arthritis [33] (Figure 3) This tracer has proven to be useful for arthritis imaging in the past but provides limited insight into the disease process. As evident from clinical trials, uptake of radiolabeled monoclonal anti-CD3 antibodies (OKT-3), which target all T cells, was detectable in inflamed joints of patients with RA and levels correlated with inflammation scores from physical examination [46,47,48]. Studies on the specificity of the antibody signal yielded conflicting results [73], but this specificity
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