[⁶⁸Ga]Pentixafor PET/MR imaging of chemokine receptor 4 expression in the human carotid artery

Purpose: Type 4 chemokine receptor (CXCR4) plays an important role in immune cell migration during the atherosclerosis progression. We aimed to evaluate [⁶⁸Ga]Pentixafor positron emission tomography (PET) in combination magnetic resonance imaging (MRI) for in vivo quantification of CXCR4 expression in carotid plaques. Methods: Seventy-two patients with lymphoma were prospectively scheduled for whole body [⁶⁸Ga]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 [⁶⁸Ga]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. Results: At hybrid PET/MRI, we observed significantly increased [⁶⁸Ga]Pentixafor uptake in mildly (mean TBR_max = 1.57 ± 0.27, mean SUV_max = 2.51 ± 0.39), moderately (mean TBR_max = 1.64 ± 0.37, mean SUV_max = 2.61 ± 0.55) and severely eccentric carotids (mean TBR_max = 1.55 ± 0.26, mean SUV_max = 2.40 ± 0.44) as compared to non-eccentric carotids (mean TBR_max = 1.29 ± 0.21, mean SUV_max = 1.77 ± 0.42) (p ≤ 0.05). 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: In vivo evaluation of CXCR4 expression in carotid atherosclerotic lesions is feasible using [⁶⁸Ga]Pentixafor PET/MRI. In atherosclerotic plaque tissue, CXCR4 expression might be used as a surrogate marker for inflammatory atherosclerosis.