Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica

Abstract

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two interrelated inflammatory diseases affecting patients above 50 years of age. Patients with GCA suffer from granulomatous inflammation of medium- to large-sized arteries. This inflammation can lead to severe ischemic complications (e.g., irreversible vision loss and stroke) and aneurysm-related complications (such as aortic dissection). On the other hand, patients suffering from PMR present with proximal stiffness and pain due to inflammation of the shoulder and pelvic girdles. PMR is observed in 40–60% of patients with GCA, while up to 21% of patients suffering from PMR are also affected by GCA. Due to the risk of ischemic complications, GCA has to be promptly treated upon clinical suspicion. The treatment of both GCA and PMR still heavily relies on glucocorticoids (GCs), although novel targeted therapies are emerging. Imaging has a central position in the diagnosis of GCA and PMR. While [18F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) has proven to be a valuable tool for diagnosis of GCA and PMR, it possesses major drawbacks such as unspecific uptake in cells with high glucose metabolism, high background activity in several non-target organs and a decrease of diagnostic accuracy already after a short course of GC treatment. In recent years, our understanding of the immunopathogenesis of GCA and, to some extent, PMR has advanced. In this review, we summarize the current knowledge on the cellular heterogeneity in the immunopathology of GCA/PMR and discuss how recent advances in specific tissue infiltrating leukocyte and stromal cell profiles may be exploited as a source of novel targets for imaging. Finally, we discuss prospective novel PET radiotracers that may be useful for the diagnosis and treatment monitoring in GCA and PMR.

Contribution of pathogenic T helper 1 and 17 cells to bursitis and tenosynovitis in polymyalgia rheumatica

“…In order to test these hypotheses, it would be interesting to extend the current tissue analyses to tendons and muscles of patients with PMR. As sampling of fragile tendons might prove difficult, novel imaging techniques with immune cell specific tracers could potentially aid the investigations of these structures in PMR ( 49 ).…”

Update on Imaging of Inflammatory Arthritis and Related Disorders

“…Macrophage can also be labeled in vivo via the folate receptor, the translocator protein (TSPO, previously known as a peripheral benzodiazepine receptor CD68) or the macrophage mannose receptor (MMR, CD206; reviewed in van der Geest et al, 2022). 20 This will be elaborated further.…”

Role of18F-FDG PET/CT in Large Vessel Vasculitis and Polymyalgia Rheumatica

“…Immuno-PET tracers, binding to specific immune cell subsets, could potentially be more accurate than conventional 18 F-FDG for treatment monitoring of patients with LV-GCA (57,58). However, further understanding regarding immune cell subsets in vasculitic lesions is needed for better selection of tracers and targets for tracer development.…”