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Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.

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 ?B and its ligand, chemokine receptors, vascular cell adhesion molecule-1, ?V?? integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.

SUBMITTER: Put S

PROVIDER: S-EPMC4061725 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.

Put Stéphanie S Westhovens René R Lahoutte Tony T Matthys Patrick P

Arthritis research & therapy 20140415 2

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 ...[more]

PMID: 25099015

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Project description:Introduction:Comorbidities influence the prognosis, clinical outcomes, disease activity, and treatment response in rheumatoid arthritis (RA). RA patients have a high-comorbidity burden necessitating their study. Comorbidity indices are used to measure comorbidities and to study their impacts on different outcomes. A large number of such indices are used in clinical research. Some indices have been specifically developed in RA patients. Aim:This review aims to provide an overview of generic and specific comorbidity indices commonly used in RA research. Methods:We performed a critical literature review of comorbidity indices in RA using the PubMed database. Results/discussion:This non-systematic literature review provides an overview of generic and specific comorbidity indices commonly used in RA studies. Some of the older but commonly used comorbidity indices like the Charlson comorbidity index and the Elixhauser comorbidity measure were primarily developed to estimate mortality risk from comorbid diseases. They were not specifically developed for RA patients but have been widely used in rheumatology comorbidity measurement. Of the many comorbidity indices available, only the rheumatic disease comorbidity index (RDCI) and the multimorbidity index have been specifically developed in RA patients. The functional comorbidity index was developed to look at functional disability and has been used in RA patients considering that morbidity is more important than mortality in such patients. While there is limited data comparing these indices, available evidence seems to favor the use of RDCI as it predicts mortality, hospitalization, disability, and healthcare utilization. The choice of the index, however, depends on several factors such as the population under study, outcome of interest, and sources of data. More research is needed to study the RA-specific comorbidity measures to make evidence-based recommendations for the choice of a comorbidity measure.

Project description:BackgroundInterleukin-7 receptor alpha (IL-7Rα) represents a biomarker with potential applications in rheumatoid arthritis (RA) diagnosis and therapy. We have therefore searched by phage display potential IL-7Rα specific peptides with the primary goal being to develop in vivo molecular imaging tools.MethodsIL-7Rα-targeted peptides were searched within a disulfide-constrained combinatorial phage displayed library of random linear heptapeptides. The apparent dissociation constant (Kd) and half maximal inhibition constant (IC50) were estimated for phage clones and synthesized peptides by ELISA. We used 5-Aza-2'-deoxycytidine (ADC)-stimulated Jurkat cells and human synovial tissue from patients with RA for in vitro characterization of peptides. For molecular imaging studies performed by magnetic resonance imaging (MRI), experimental arthritis was induced in DBA/1 male mice by immunization with an emulsion of complete Freund's adjuvant and type II collagen from chicken sternal cartilage.ResultsAfter several steps of phage display and peptide screening, two IL-7Rα-specific heptapeptides (P258 and P725) were selected from the initial library, based on their affinity for the target (extracellular domain of IL-7Rα, which contains a fibronectin type III repeat-like sequence). P258 (a linear peptide obtained by removing the Cys-constraint) had the lowest affinity for fibronectin itself and was therefore proposed for molecular imaging. After grafting to ultra-small superparamagnetic particles of iron oxide (USPIO), P258 produced a strong negative contrast on MRI in mice with collagen-induced arthritis (CIA), even at 2 hours post injection. The co-localization of USPIO-P258 with IL-7Rα-expressing cells in the synovial tissue from CIA mice and its ability to discriminate the level of IL-7R expression and the disease severity confirmed its efficacy as an in vivo IL-7Rα imaging agent. Interestingly, the cyclic peptide (P725), which was less adequate for molecular imaging because of higher affinity for fibronectin, had a strong ability to compete with IL-7 for the IL-7Rα binding sites, making it a potential candidate for blocking applications. Accordingly, P725 prevented the signal transducer and activator of transcription 5 (STAT5) activation induced by IL-7 in ADC-stimulated Jurkat cells.ConclusionsThe two peptides identified in this work demonstrate that IL-7Rα targeting in RA presents potential applications for in vivo molecular imaging and putative blocking purposes.

Dataset Information

Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.

Publications

Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques.

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