PurposeType 4 chemokine receptor (CXCR4) plays an important role in immune cell migration during the atherosclerosis progression. We aimed to evaluate [Ga-68]Pentixafor positron emission tomography (PET) in combination magnetic resonance imaging (MRI) for in vivo quantification of CXCR4 expression in carotid plaques.MethodsSeventy-two patients with lymphoma were prospectively scheduled for whole body [Ga-68]Pentixafor PET/MRI with an additional T2-weighted carotid sequence. Volumes of interest (VOIs) were drawn along the carotid bifurcation regions, and the maximum tissue-to-blood ratios (TBR) of [Ga-68]Pentixafor uptake were calculated. Lesions were categorized into non-eccentric (n=27), mild eccentric (n=67), moderately (n=41) and severely (n=19) eccentric carotid atherosclerosis. A different cohort of symptomatic patients (n=10) with carotid stenosis scheduled for thrombendarterectomy (TEA) was separately imaged with 3T MRI with dedicated plaque sequences (time of flight, T1-, and T2-weighted). MRI findings were correlated with histochemical assessment of intact carotid plaques.ResultsAt hybrid PET/MRI, we observed significantly increased [Ga-68]Pentixafor uptake in mildly (mean TBRmax=1.570.27, mean SUVmax=2.51 +/- 0.39), moderately (mean TBRmax=1.64 +/- 0.37, mean SUVmax=2.61 +/- 0.55) and severely eccentric carotids (mean TBRmax=1.55 +/- 0.26, mean SUVmax=2.40 +/- 0.44) as compared to non-eccentric carotids (mean TBRmax=1.29 +/- 0.21, mean SUVmax=1.77 +/- 0.42) (p0.05). Histological findings from TEA confirmed that prominent CXCR4 expression was localized within inflamed atheromas and preatheromas. Co-localization of cellular CXCR4 and CD68 expression in the plaque was observed by immunofluorescence staining.Conclusions p id=Par4 In vivo evaluation of CXCR4 expression in carotid atherosclerotic lesions is feasible using [Ga-68]Pentixafor PET/MRI. In atherosclerotic plaque tissue, CXCR4 expression might be used as a surrogate marker for inflammatory atherosclerosis.