A new PET tracer that lights up inflamed blood vessels could become a much-needed biomarker for giant cell arteritis, a new human study suggests, having tracked vascular disease activity and faded with the advent of steroid therapy.
Why is measuring vasculitis activity so difficult?
Measuring giant cell arteritis (GCA) activity remains an ongoing problem, because current clinical, laboratory, and imaging measures lack the specificity of in vivo vasculitis. Therefore, researchers sought to find a biomarker specific to inflammation. The tracer studied targets vascular adhesion protein-1 (VAP-1), a molecule that is transported to the vessel surface during inflammation.
The first imaging experiment in humans
In this first-in-human proof-of-concept study, eight patients with newly diagnosed GCA underwent treatment [68Ga]Ga-DOTA-Siglec-9 PET/CT combined with vascular ultrasound was compared in eight relapsed patients and eight healthy subjects. Tracer uptake, measured as SUVmean and SUVmax, was quantified across the aortic shoulder and hip, supraaortic, and extravascular shoulder and hip regions. Soluble VAP-1 (sVAP-1) and matrix metalloproteinases MMP2, MMP3, and MMP9 have been evaluated in patients and controls as candidate markers of vascular inflammation.
A biomarker that tracks giant cell arteritis activity
Tracer uptake correlated positively with subclavian artery wall thickness measured by ultrasound (r = 0.67, p = 0.035). Prednisolone exposure was inversely related 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) compared to relapsed patients (819.9 pg/ml; p = 0.0145) and controls (726.1 pg/ml; p = 0.0446). In contrast, MMP9 was significantly higher in newly diagnosed disease (79.0 ng/ml) than in relapsed patients (19.7 ng/ml; p = 0.0087) and controls (5.6 ng/ml; p = 0.0016), with MMP2 similarly elevated. MMP2 and MMP3 were inversely associated with tracer uptake, eg in 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 ameliorate with steroid treatment, making it a promising biomarker of inflammation. The pattern of decreased sVAP-1 and inverse MMP correlations suggests a functional VAP-1/MMP axis behind the imaging signal. However, they cautioned that the group was too small, and noted that uptake in patients with polymyalgia rheumatica suggests broader use across the GCA spectrum, although larger studies are needed.
reference
Pizzina CM et al. [68Ga]Ga-DOTA-Siglec-9 PET/CT in newly diagnosed giant cell arteritis: a molecular imaging biomarker of inflammation and response to therapy. RMD is open. 2026;12:e006633.
Featured image: Valerii Apetroaiei on Adobe Stock
