Abstract
PurposeType 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.MethodsSeventy-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.ResultsAt hybrid PET/MRI, we observed significantly increased [68Ga]Pentixafor uptake in mildly (mean TBRmax = 1.57 ± 0.27, 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) (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.ConclusionsIn 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.
Highlights
Methods and materialsAtherosclerotic plaques develop from a thickening of the vascular wall due to progressive accumulation of inflammatory cells and oxidized lipid components in the arterial intima [1]
We discovered that the elevated CXCR4 expression in the atheromas was localized in adipose tissue (Fig. 4), and CXCR4 expression mostly co-localized with CD3 (T-cells) and CD68 expression by immunofluorescence staining (Fig. 5)
We observed relatively low [68Ga]Pentixafor carotid uptake in non-stenosis lesions compared to eccentric atherosclerotic lesions, which showed significantly higher CXCR4 expression
Summary
Atherosclerotic plaques develop from a thickening of the vascular wall due to progressive accumulation of inflammatory cells and oxidized lipid components in the arterial intima [1]. High-resolution MRI scans, including time of flight (TOF) and T1- and T2-weighted imaging due to the high contrast to soft tissue, was shown to be sensitive for the characterization of atherosclerosis [4], including identification of lipid components, such as intra-plaque hemorrhage [5], fibrous cap [6], calcification or the lipid core [7]. In addition to MRI anatomical imaging of plaques, the use of specific radiotracers to measure intra-plaque inflammatory targets or atherosclerosis progression [8] by PET has become a major complementary approach for MRI diagnostics [9]
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