Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque Using ⁶⁸Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden

The CXC-motif chemokine receptor 4 (CXCR4) represents a promising target for molecular imaging of different CXCR4-positive cell types in cardiovascular diseases such as atherosclerosis and arterial wall injury. The aim of this study was to assess the prevalence, pattern, and clinical correlates of arterial wall accumulation of ⁶⁸Ga-pentixafor, a specific CXCR4 ligand for PET. <b>Methods:</b> The data for 51 patients who underwent ⁶⁸Ga-pentixafor PET/CT for noncardiovascular indications were retrospectively analyzed. Tracer accumulation in the vessel wall of major arteries was analyzed qualitatively and semiquantitatively by blood-pool-corrected target-to-background ratios. Tracer uptake was compared with calcified plaque burden and cardiovascular risk factors. <b>Results:</b> Focal arterial uptake of ⁶⁸Ga-pentixafor was seen at 1,411 sites in 51 (100%) of patients. ⁶⁸Ga-pentixafor uptake was significantly associated with calcified plaque burden (<i>P</i> < 0.0001) and cardiovascular risk factors including age (<i>P</i> < 0.0001), arterial hypertension (<i>P</i> < 0.0001), hypercholesterolemia (<i>P</i> = 0.0005), history of smoking (<i>P</i> = 0.01), and prior cardiovascular events (<i>P</i> = 0.0004). Both the prevalence (<i>P</i> < 0.0001) and the signal intensity (<i>P</i> = 0.009) of ⁶⁸Ga-pentixafor uptake increased as the number of risk factors increased. <b>Conclusion:</b>⁶⁸Ga-pentixafor PET/CT is suitable for noninvasive, highly specific PET imaging of CXCR4 expression in the atherosclerotic arterial wall. Arterial wall ⁶⁸Ga-pentixafor uptake is significantly associated with surrogate markers of atherosclerosis and is linked to the presence of cardiovascular risk factors. ⁶⁸Ga-pentixafor signal is higher in patients with a high-risk profile and may hold promise for identification of vulnerable plaque.