Systematic Review: Targeted Molecular Imaging of Angiogenesis and Its Mediators in Rheumatoid Arthritis

Abstract

Extensive angiogenesis is a characteristic feature in the synovial tissue of rheumatoid arthritis (RA) from a very early stage of the disease onward and constitutes a crucial event for the development of the proliferative synovium. This process is markedly intensified in patients with prolonged disease duration, high disease activity, disease severity, and significant inflammatory cell infiltration. Angiogenesis is therefore an interesting target for the development of new therapeutic approaches as well as disease monitoring strategies in RA. To this end, nuclear imaging modalities represent valuable non-invasive tools that can selectively target molecular markers of angiogenesis and accurately and quantitatively track molecular changes in multiple joints simultaneously. This systematic review summarizes the imaging markers used for single photon emission computed tomography (SPECT) and/or positron emission tomography (PET) approaches, targeting pathways and mediators involved in synovial neo-angiogenesis in RA.

Update on Imaging of Inflammatory Arthritis and Related Disorders

“…60 Other Potential Targets for PET Imaging of RA Other potential relevant targets for RA imaging and monitoring include binding sites on T-cell subsets, B-cells, fibroblasts and neutrophils, angiogenesis and endothelial-cell differentiation, and may originate from the cancer-immunology field. [61][62] PET tracer development and in vivo evaluation for these targets are mostly in preclinical phase of investigation.…”

Increased Imaging Ligand Hydrophilicity and Improved Pharmacokinetic Properties Provides Enhanced In Vivo Targeting of Fibroblast Activation Protein

“…Targeted molecular imaging has the potential to address these limitations and detect joint in ammation in a minimally invasive manner 9,10 . Towards that end, researchers are exploring a variety of targeted agents for RA, including extracellular matrix proteins and cell-surface receptors [11][12][13] . Activated synovial broblasts and immune cells produce in ammatory cytokines, which are hypothesized to drive RA development and progression 14,15 .…”

Computational Fluid Dynamics (CFD) Model for Analysing the Role of Shear Stress in Angiogenesis in Rheumatoid Arthritis

“…Owing to the involvement of many different variables, the pathophysiology of RA is still not fully understood [4]. However, angiogenesis is crucial to the progression of RA and results in the formation of new blood vessels [5][6][7][8]. Under physiological conditions, angiogenesis is governed by a complex, balanced network of chemical and mechanical cues, which maintain vital physiological functions [9].…”

“…Various sources have reported increased angiogenesis in RA patients, which can be detected at the point of clinical diagnosis [6]. RA produces a radically altered synovial composition with a reduced viscosity [11].…”

“…This enables pannus formation in the affected joint [3,10,[12][13][14][15][16]. The environment in the pannus is hypoxic and inflammatory, necessitating increased angiogenesis to supply oxygen and nutrients [6,14,17]. Another view is that angiogenesis, a process natural to the body, drives RA through the development and maintenance of the pannus in an environment that upregulates vascular endothelial growth factor (VEGF) [7,10,12].…”