Abstract Background PET imaging in giant cell arteritis (GCA) is crucial for diagnosis. New tracers such as C-X-C motif chemokine receptor 4 (CXCR4) enable to directly visualize inflammatory cells as they are expressed on leukocytes. We aimed to test the value of CXCR4-targeted PET in GCA. Methods Ten treatment-naïve patients with confirmed large-vessel GCA underwent both 18 FFDG and 68 GaPentixaFor PET/CT scans within a median of two days, without any therapy in between. Thirteen arterial segments per patient were analyzed. Visual interpretation and quantitative target-to-background ratios (TBR; arterial SUVmax divided by superior vena cava SUVmean) were calculated, including per-patient mean TBRs. Five patients without clinical or diagnostic evidence of vasculitis served as Non-GCA controls. Flow cytometry was used to quantify CXCR4 expression on leukocyte subsets, reported as normalized median fluorescence intensity (NMFI). Results All GCA patients showed positive scan findings on both 18 FFDG and 68 GaPentixaFor PET/CT. Mean vascular TBRs were 2.43 ± 0.90 for FDG and 1.76 ± 0.76 for PentixaFor ( P = 0.07), indicating similar large-vessel uptake. Segment-level analysis showed no significant differences in 10/13 vascular regions, although FDG uptake was higher in selected arteries. PentixaFor TBR was significantly lower in Non-GCA controls (1.15 ± 0.10 vs. 1.76 ± 0.76; P = 0.01), supporting its specificity for inflammation. Blood pool SUVmean did not differ, suggesting minimal signal spill-in. CXCR4 expression was highest on naïve T-helper cells and monocytes. Conclusions CXCR4-targeted 68 GaPentixaFor PET/CT provides an imaging pattern comparable to 18 FFDG PET/CT in untreated GCA and reliably differentiates between inflamed and non-inflamed vessels. These findings support CXCR4 PET as a promising, mechanistically grounded imaging approach that merits further evaluation in larger patient cohorts. Clinical trial number ClinicalTrials.gov NCT05604482. Registered 3 November 2022.
Fröhlich et al. (Wed,) studied this question.