CXCR4-Upregulation in Atherosclerotic Plaques is Attenuated by the Anti-Inflammatory and Anti-Fibrotic Drug Pirfenidone

Ziel/Aim Molecular imaging of the CXC-motif chemokine receptor CXCR4 with ⁶⁸ Ga-pentixafor PET/CT has emerged as a promising tool for in vivo characterization of atherosclerotic plaque biology representing a promising target for molecular imaging of different CXCR4-positive cell types in atherosclerosis. However, few studies have shown whether the CXCR4 signal in plaques can be modulated by therapeutic interventions.

Methodik/Methods A secondary analysis of vessel wall lesions was performed in 16 patients with idiopathic pulmonary fibrosis (IPF) who had undergone serial ⁶⁸Ga-pentixafor PET/CT before and 6–12 weeks after initiation of treatment with pirfenidone, a drug with broad anti-oxidant, anti–inflammatory and anti-fibrotic activity. In both studies, CXCR4-positive atherosclerotic lesions in the vessel wall of all major arteries, calcified plaque (CP) burden and global CXCR4 expression of the aorta descendens were compared intra- and interindividually, and matched with pulmonary treatment response to pirfenidone. Tracer uptake was quantified using standardized uptake values (SUVs) and target-to-background ratios (TBRs).

Ergebnisse/Results Pirfenidone treatment significantly reduced the number of focally increased ⁶⁸Ga-pentixafor uptake sites in the major arteries (baseline (BL): 306 lesions, post therapy (PT) 239 lesions; p = 0.007), mean SUV_max (BL: 3.6 ± 0.7, PT: 3.2 ± 0.7, p = 0.011) and mean TBRmax (BL: 2.0 ± 0.5, PT: 1.8 ± 0.4, p = 0.013). Global CXCR4 expression of the aorta descendens trended to decrease (mean TBRmax: BL: 1.6 ± 0.3, PT: 1.5 ± 0.2, p = 0.070). CP burden remained unchanged (BL: 1781 CPs, PT: 1789 CPs; p = ns). Vascular changes of CXCR4 signal were independent of lung function improvement.

Schlussfolgerungen/Conclusions ⁶⁸Ga-pentixafor PET/CT is suitable for noninvasive identification of changes in atherosclerotic plaque biology in response to therapeutic intervention. Independent of its beneficial effect on lung function in IPF, pirfenidone also influences CXCR4 expression in vessel wall lesions.