Matthias Froehlich1, Sebastian E. Serfling2, Michael Gernert3, Konstanze V. Guggenberger4, Takahiro Higuchi2, Samuel Samnick2, Marc Schmalzing5, Andreas K. Buck2, Thorsten Bley4 and Rudolf A. Werner2, 1Rheumatology/Clinical Immunology, Department of Internal Medicine II, University of Würzburg, Würzburg, Germany, 2Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany, 3Medical Department II, Rheumatology, University Hospital Würzburg, Würzburg, Germany, 4Institute of Diagnostic and Interventional Radiology, University Hospital Würzburg, Würzburg, Germany, 5University Hospital, Rheumatology/Clinical Immunology, Department of Internal Medicine II, Würzburg, Germany
Background/Purpose: 2-[18F]fluoro-2-deoxy-D-glucose(FDG) is the reference PET radiotracer for detecting inflammation in giant cell arteritis (GCA). C-X-C motif chemokine receptor 4 (CXCR4)-directed PET, however, allows for targeting leukocyte subsets, thereby providing a direct visualization of active inflammation. We aimed to report initial results from a Phase II trial applying chemokine receptor-targeted imaging in patients with newly diagnosed GCA (NCT05604482).
Methods: Nine treatment-naïve individuals with confirmed GCA underwent PET/CT imaging with both FDG and [68Ga] PentixaFor (PXF). For each PET, a total of 13 arterial segments per patient were analyzed. In addition, eight joints were examined for concurrent polymyalgia rheumatica. We compared both scans on a visual (using PETVAS) and quantitative level (by calculating the target-to-background ratio [TBR], with blood pool as reference). Flow cytometry determined quantitative CXCR4 expression on leukocytes in peripheral blood by calculating a normalized median fluorescence intensity (NMFI) scoring (with CXCR4 antibody isotype serving as control). Quantitative PET results were then correlated with NMFI.
Results: At the visual level, PETVAS of FDG (25.62 ± 5.61) was comparable with PXF (21.33 ± 3.5, P=0.07). The TBR of FDG (2.41 ± 0.96) was also not significantly different from that of PXF (1.8 ± 0.8, P=0.11). The interquartile ranges (IQR) for PEN (IQR, 0.48), however, were lower than for FDG (IQR, 1.5), suggesting lower scatter and improved accuracy for PXF-based quantitative read-outs. Comparable results were also recorded for joints (PEN: IQR, 0.25; FDG: IQR, 0.5). Flow cytometry showed broad expression of CXCR4 on leukocytes. Subpopulations with the highest CXCR4 expression were naive B and T cells, followed by basophils. NMFI and PXF-based quantification showed significant correlations with basophils in the aorta, with the most prominent association for the abdominal segment (r=0.85, P=0.03).
Conclusion: Quantification of the CXCR4-targeted PET radiotracer PXF was comparable to FDG for assessing vessel wall and joint inflammation. Thus, PXF PET may be incorporated for image-guided, anti-inflammatory strategies in patients with newly diagnosed GCA.
M. Froehlich: None; S. Serfling: None; M. Gernert: None; K. Guggenberger: None; T. Higuchi: None; S. Samnick: None; M. Schmalzing: AbbVie, 2, 6, Boehringer Ingelheim, 2, 5, 6, Chugai/Roche, 2, EUSA-Pharma, 2, 6, Galapagos, 2, 5, 6, Hexal/Sandoz, 2, Janssen-Cilag, 2, 6, Lilly, 2, onkowissen.de, 2, UCB, 2, 5; A. Buck: None; T. Bley: None; R. Werner: None.
