Novel PET/CT tracers for large-vessel vasculitis: molecular imaging of immune cell recruitment, myeloid activation and vascular remodelling in giant cell arteritis and Takayasu's arteritis

Over the past decade, positron emission tomography (PET) has become an important part of the management of large-vessel vasculitis (LVV). Current clinical practice relies predominantly on [18F]fluorodeoxyglucose ([18F]FDG) PET combined with computed tomography (CT) for anatomical localisation. Although [18F]FDG PET/CT shows high specificity and good sensitivity for primary diagnosis, persistent vascular uptake during clinical remission limits its specificity for relapse assessment and complicates longitudinal monitoring. Alongside technological advances in PET hardware, an expanding portfolio of alternative radiotracers has emerged to probe more specific inflammatory pathways and cell-associated processes.This narrative review summarises the most informative clinical evidence currently available for novel PET tracers in giant cell arteritis (GCA) and Takayasu's arteritis (TAK). Targets related to immune cell recruitment and vascular inflammation include the vascular adhesion protein-1 (VAP-1)/sialic-acid-binding immunoglobulin-like lectin-9 (Siglec-9) axis, assessed by [68Ga] Ga-DOTA-Siglec-9. Similarly, C-X-C chemokine receptor 4 (CXCR4) imaging with [68Ga]PentixaFor has been explored as an approach to capture chemokine-mediated immune cell trafficking. For the assessment of myeloid activation, somatostatin receptor subtype 2 (SSTR2) imaging using [68Ga] DOTATATE or [18F]FET-βAG-TOCA has been explored as an approach to differentiate active from inactive disease. Imaging of the 18 kDa translocator protein (TSPO), a mitochondrial outer membrane protein associated with cellular stress and myeloid activation, seeks to provide a complementary inflammation- and stress-related read-out, although its clinical applicability is influenced by ligand-specific performance and genotype-dependent binding. Finally, fibroblast activation protein (FAP)-targeted PET with fibroblast activation protein inhibitors (FAPI, e.g. [68Ga]-FAPI-46) has been investigated to visualise fibroblast activation and vascular remodelling, with persistent uptake during clinical remission potentially indicating ongoing tissue repair or structural remodelling.