CXCR4-targeted PET/CT in early systemic sclerosis-associated interstitial lung disease: a prospective...

Distinguishing active inflammatory or remodeling-associated processes from irreversible fibrosis in systemic sclerosis remains challenging using conventional imaging modalities. The tracer [⁶⁸Ga]Pentixafor targets the C-X-C motif chemokine receptor 4 (CXCR4) which is expressed on leukocytes. Uptake of [⁶⁸Ga]Pentixafor may provide complementary biological information on CXCR4-associated inflammatory and remodeling activity.

This prospective cohort study included patients with early SSc (disease duration ≤ 5 years) and preexisting interstitial lung disease. All patients underwent [⁶⁸Ga]Pentixafor-PET/CT imaging. Normalized [⁶⁸Ga]Pentixafor uptake was quantified using the target-to-background ratio (TBR). Follow-up data on disease progression was collected. A control group comprised patients with giant cell arteritis.

Twelve patients with SSc were included. The highest [⁶⁸Ga]Pentixafor uptake was observed in the hilar and mediastinal lymph nodes, in fibrotic lung regions, and in the left ventricular myocardium. In all three regions, a significantly higher [⁶⁸Ga]Pentixafor uptake was measured in SSc compared to controls (median TBR of lymph nodes 3.5 [IQR 2.7 - 4.3] vs 1.6 [1.3 - 2.0] p < 0.0001; inferior lung lobes 2.3 [1.6 - 2.8] vs 0.8 [0.7 - 1.0], p < 0.0001; and left ventricle 2.0 [1.4 - 2.4] vs 1.3 [1.1 - 1.5], p = 0.0178). Patients who developed progressive lung disease during follow-up showed a higher [⁶⁸Ga]Pentixafor uptake compared to non-progressive patients reaching statistical significance in the left ventricle (TBR of progressive vs non-progressive patients: 2.5 (2.1 - 3.3) vs 1.5 (1.3 - 2.1), p = 0.0283) and showing a numerical increase in fibrotic lung regions (2.8 (2.2 - 3.3) vs 1.7 (1.1 - 2.8), p = 0.1535).

These findings provide proof-of-concept evidence that CXCR4-targeted PET/CT may visualize biologically active inflammatory and/or remodeling processes in early-stage SSc-ILD.