Abstract
Early diagnosis and monitoring of disease progress are of significant importance in the effective treatment of rheumatoid arthritis (RA), because the continuing inflammation can lead to irreversible joint damage and systemic complications. However, applying imaging modalities for the prognosis of RA remains challenging, because no tissue‐specific guidelines are available to monitor the progressive course of RA. In this study, fluorometric imaging of RA is reported using bioengineered targeted agents of the blood vessel, bone, and cartilage in combination with the customized optical fluorescence imaging system. Separate but simultaneous tissue‐specific images of synovitis, cartilage destruction, and bone resorption are obtained from a mouse model of RA, which allows quantification of the prognosis of diseases at each stage. Thus, the fluorometric imaging of RA by using tissue‐specific contrast agents plays a key role in the systemic treatment of RA by monitoring structural damage and disease progression.
Highlights
Diagnosis and monitoring of disease progress are of significant imporhas an insidious onset and principally tance in the effective treatment of rheumatoid arthritis (RA), because the continuing inflammation can lead to irreversible joint damage and systemic complications
Separate but simultaneous tissue-specific images of synovitis, cartilage destruction, and bone resorption are obtained from a mouse model of RA, which allows quantification of the prognosis of diseases at each is generally established by physical examination, joint radiographs, serological tests, and, more recently, by musculoskeletal ultrasonography and magnetic resonance imaging (MRI).[5,6]
The inflammation can be further divided into three different stages, and such transitional stages were assessed by dual-channel optical imaging with the following tissue-specific NIR fluorophores (Figure 1a): 1) Dex700 (700 nm NIR)[16] and indocyanine green (ICG) (800 nm NIR) were prepared to assess synovitis severity; and 2) C700-OMe (700 nm NIR)[10] and P800SO3
Summary
The inflammation can be further divided into three different stages (i.e., acute, chronic, and longstanding stages), and such transitional stages were assessed by dual-channel optical imaging with the following tissue-specific NIR fluorophores (Figure 1a): 1) Dex700 (700 nm NIR)[16] and ICG (800 nm NIR) were prepared to assess synovitis severity; and 2) C700-OMe (700 nm NIR)[10] and P800SO3 NIR)[12] were synthesized to monitor the destruction process of cartilage and bone, respectively. Both C700-OMe and P800SO3 are composed of polymethine backbone and structure-inherent targeting moieties.[10,12] All NIR fluorophores are high extinction coefficients and high quantum yields (QYs), which together minimize tissue autofluorescence and maximize the signalto-background ratio (SBR; see Figure S1, Supporting Information). The specific design of the three light sources (i.e., white light, 660 nm laser, and 760 nm laser) and filtration of emitted light made the aforementioned four NIR fluorophores amenable to targeted tissue imaging.[17,18]
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