A NOVEL PET tracer that lights up inflamed blood vessels could become a much-needed biomarker for giant cell arteritis, a first-in-human study suggests, after it tracked vascular disease activity and faded as steroid treatment took hold.
Why Measuring Vasculitis Activity Is So Hard
Gauging giant cell arteritis (GCA) activity remains a persistent problem, because current clinical, laboratory, and imaging measures lack specificity for live vascular inflammation. Researchers have therefore sought an inflammation-specific biomarker. The tracer studied targets vascular adhesion protein-1 (VAP-1), a molecule shuttled to the vessel surface during inflammation.
A First-in-Human Imaging Experiment
In this proof-of-concept, first-in-human study, eight patients with newly diagnosed GCA underwent [68Ga]Ga-DOTA-Siglec-9 PET/CT alongside vascular ultrasound, and were compared with eight relapsing patients and eight healthy controls. Tracer uptake, measured as SUVmean and SUVmax, was quantified across aortic, supra-aortic, and extravascular shoulder and hip regions. Soluble VAP-1 (sVAP-1) and matrix metalloproteinases MMP2, MMP3, and MMP9 were assayed in patients and controls as candidate markers of vascular inflammation.
A Biomarker That Tracks Giant Cell Arteritis Activity
Tracer uptake correlated positively with ultrasound-measured subclavian artery wall thickness (r=0.67, p=0.035). Prednisolone exposure was inversely linked to vascular uptake, more strongly for SUVmean than SUVmax (SUVmean r=-0.51, p=0.043; SUVmax r=-0.62, p=0.010). Soluble VAP-1 was lower in newly diagnosed GCA (502.7 pg/mL) than in relapsing patients (819.9 pg/mL; p=0.0145) and controls (726.1 pg/mL; p=0.0446). By contrast, MMP9 was markedly higher in newly diagnosed disease (79.0 ng/mL) than in relapsing patients (19.7 ng/mL; p=0.0087) and controls (5.6 ng/mL; p=0.0016), with MMP2 similarly raised. MMP2 and MMP3 were inversely associated with tracer uptake, for example at the aortic arch (r=-0.59, p=0.027).
The authors concluded that [68Ga]Ga-DOTA-Siglec-9 PET/CT can detect vascular inflammation in giant cell arteritis and dims with steroid treatment, positioning it as a promising inflammation-specific biomarker. The pattern of reduced sVAP-1 and inverse MMP associations points to a functional VAP-1/MMP axis behind the imaging signal. They cautioned, however, that the cohort was very small, and noted that uptake in patients with polymyalgia rheumatica hints at wider use across the GCA spectrum, though larger studies are needed.
Reference
Petzinna SM et al. [68Ga]Ga-DOTA-Siglec-9 PET/CT in newly diagnosed giant cell arteritis: an inflammation-specific, treatment-responsive molecular imaging biomarker. RMD Open. 2026;12:e006633.
Featured image: Valerii Apetroaiei on Adobe Stock
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