Purpodre The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [Ga-68]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [Ga-68]Pentixafor PET/MRI. Methods Thirty-eight oncology patients underwent [Ga-68]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUVmax) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [Ga-68]Pentixafor PET/MRI was assessed in seven patients with a follow-up exanimation by Pearson's regression and Bland-Altman plots analysis. Results Thirty-four of 38 patients showed 611 focal [Ga-68]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBRmax were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 +/- 0.3) as compared to women (1.7 +/- 0.2; p < 0.05). Patients with mean TBRmax > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBRmax <= 1.7. [Ga-68]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBRmax values of plaque lesions (TBR(baseline)1.8 +/- 0.3 vs TBR(follow-up)1.8 +/- 0.3) (p = 0.9). Conclusion Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [Ga-68]Pentixafor in characterization of atherosclerosis.