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Background <p>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.</p> Methods <p>Ten treatment-naïve patients with confirmed large-vessel GCA underwent both [<sup>18</sup>F]FDG and [<sup>68</sup>Ga]PentixaFor 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).</p> Results <p>All GCA patients showed positive scan findings on both [<sup>18</sup>F]FDG and [<sup>68</sup>Ga]PentixaFor PET/CT. Mean vascular TBRs were 2.43 ± 0.90 for FDG and 1.76 ± 0.76 for PentixaFor (<i>P</i> = 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; <i>P</i> = 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.</p> Conclusions <p>CXCR4-targeted [<sup>68</sup>Ga]PentixaFor PET/CT provides an imaging pattern comparable to [<sup>18</sup>F]FDG 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.</p> Clinical trial number <p>ClinicalTrials.gov NCT05604482. Registered 3 November 2022.</p>

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Establishing C-X-C motif chemokine receptor 4 as a novel imaging target in giant cell arteritis

  • 期刊论文

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  • 发表日期：

    2026年2月11日

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  • Matthias Fröhlich,
  • Sebastian E. Serfling,
  • Michael Gernert,
  • Konstanze Guggenberger,
  • Takahiro Higuchi,
  • Elena Gerhard-Hartmann,
  • Alexander Weich,
  • Samuel Samnick,
  • Marc Schmalzing,
  • Thorsten A. Bley,
  • Andreas K. Buck,
  • Rudolf A. Werner

摘要

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 [18F]FDG and [68Ga]PentixaFor 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 [18F]FDG and [68Ga]PentixaFor 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 [68Ga]PentixaFor PET/CT provides an imaging pattern comparable to [18F]FDG 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.