Visualizing rheumatic diseases
Authors:   , Verweij Nicki Janna Francisca 
Published: January 2023

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are two types of inflammatory rheumatic diseases that are characterized by inflammation of the joints. In RA chronic inflammation leads to pain and joint swelling and, if not treated early and efficiently, is associated with progressive destruction of bone and cartilage. In AS chronic inflammation usually is located primarily in the axial skeleton, but can also manifest in peripheral joints. Just as in RA, lack of timely and efficient treatment can result in (progressive) bone formation and destruction. Historically, clinical assessment, inflammation markers in the blood and conventional radiographs are the cornerstone of both diagnosis and determination of therapeutic efficacy in inflammatory arthritis. In addition, the value of magnetic resonance imaging (MRI) and ultrasonography is being explored. However, both techniques have significant downsides in clinical application. Consequently, there is room for improvement to address the clinical needs and fill the gaps of the currently applied imaging tools.

Positron emission tomography (PET) is an imaging technique that can visualize the uptake and binding of PET tracers in affected tissues. A PET tracer consists of an agent that binds to a molecular target of interest, coupled to a positron emitting radionuclide, which makes it visible for the PET camera. At present, it is the most sensitive technique for imaging pathophysiological changes at a picomolar level. When combined with an additional anatomical modality, such as computed tomography (CT) or MRI, the molecular data can be fused with anatomical data, providing the ability to visually assess uptake in specified organs and tissues. Enhanced uptake can be assessed both visually and quantitatively. Although PET imaging is an established tool in oncology and neurology, its application in rheumatology is relatively new. This thesis focusses on the value of PET/CT for early diagnosis and therapy monitoring in rheumatic diseases, using macrophage and bone formation tracers to evaluate RA and AS, respectively. It is therefore divided into two parts.

In the first part of the thesis, the value of macrophage PET imaging in RA is explored. Macrophage PET tracers have previously demonstrated to visualize inflammatory activity in the joints of RA patients with high sensitivity. However, first generation tracers have significant downsides and large cohort studies combining PET scanning with clinical assessment are rare. The first three chapters focus on the exploration of novel, second generation macrophage tracers, and the last two chapters focus on the use of an established tracer in clinical assessment in early RA patients. In the second part, [18F]fluoride PET is investigated in AS patients. The ability of [18F]fluoride PET to visualize bone formation has been established in other medical fields. In addition, [18F]fluoride showed to be more adept at reflecting AS activity than macrophage PET tracers. However, PET/CT in AS patients has never been compared head to head with established imaging techniques such as MRI and conventional radiographs (CR), and the relation to therapy response is still unclear. The first chapter investigates the value of [18F]fluoride PET as compared with other imaging modalities, and the second chapter on the potential for predicting clinical response to therapy.

This thesis establishes the value of PET imaging in rheumatic diseases. It demonstrates potential for macrophage PET for assessment and monitoring of inflammation in RA patients and fluoride PET for imaging of bone formation in AS patients. Both techniques could provide significant additional value to the current clinical standard of disease assessment and management in RA and AS.