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Published in: European Journal of Nuclear Medicine and Molecular Imaging 8/2019

Open Access 01-07-2019 | Magnetic Resonance Imaging | Original Article

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

Authors: Xiang Li, Wei Yu, Tim Wollenweber, Xia Lu, Yongxiang Wei, Dietrich Beitzke, Wolfgang Wadsak, Saskia Kropf, Hans J. Wester, Alexander R. Haug, Xiaoli Zhang, Marcus Hacker

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 8/2019

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Abstract

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 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.

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.
Literature
4.
go back to reference Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation. 2002;106:1368–73.CrossRefPubMed Cai JM, Hatsukami TS, Ferguson MS, Small R, Polissar NL, Yuan C. Classification of human carotid atherosclerotic lesions with in vivo multicontrast magnetic resonance imaging. Circulation. 2002;106:1368–73.CrossRefPubMed
6.
go back to reference Hatsukami TS, Ross R, Polissar NL, Yuan C. Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation. 2000;102:959–64.CrossRefPubMed Hatsukami TS, Ross R, Polissar NL, Yuan C. Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging. Circulation. 2000;102:959–64.CrossRefPubMed
9.
go back to reference Rischpler C, Nekolla SG, Beer AJ. PET/MR imaging of atherosclerosis: initial experience and outlook. Am J Nucl Med Mol Imaging. 2013;3:393–6.PubMedPubMedCentral Rischpler C, Nekolla SG, Beer AJ. PET/MR imaging of atherosclerosis: initial experience and outlook. Am J Nucl Med Mol Imaging. 2013;3:393–6.PubMedPubMedCentral
21.
22.
30.
go back to reference Gupta SK, Lysko PG, Pillarisetti K, Ohlstein E, Stadel JM. Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines. J Biol Chem. 1998;273:4282–7.CrossRefPubMed Gupta SK, Lysko PG, Pillarisetti K, Ohlstein E, Stadel JM. Chemokine receptors in human endothelial cells. Functional expression of CXCR4 and its transcriptional regulation by inflammatory cytokines. J Biol Chem. 1998;273:4282–7.CrossRefPubMed
Metadata
Title
[68Ga]Pentixafor PET/MR imaging of chemokine receptor 4 expression in the human carotid artery
Authors
Xiang Li
Wei Yu
Tim Wollenweber
Xia Lu
Yongxiang Wei
Dietrich Beitzke
Wolfgang Wadsak
Saskia Kropf
Hans J. Wester
Alexander R. Haug
Xiaoli Zhang
Marcus Hacker
Publication date
01-07-2019
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 8/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-019-04322-7

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