Imaging of chemokine receptor CXCR4 expression in culprit and nonculprit coronary atherosclerotic plaque using motion-corrected [68Ga]pentixafor PET/CT | springermedicine.com

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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-10-2018 | Original Article

Imaging of chemokine receptor CXCR4 expression in culprit and nonculprit coronary atherosclerotic plaque using motion-corrected [⁶⁸Ga]pentixafor PET/CT

Authors: Thorsten Derlin, Daniel G. Sedding, Jochen Dutzmann, Arash Haghikia, Tobias König, L. Christian Napp, Christian Schütze, Nicole Owsianski-Hille, Hans-Jürgen Wester, Saskia Kropf, James T. Thackeray, Jens P. Bankstahl, Lilli Geworski, Tobias L. Ross, Johann Bauersachs, Frank M. Bengel

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 11/2018

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Abstract

Purpose

The chemokine receptor CXCR4 is a promising target for molecular imaging of CXCR4⁺ cell types, e.g. inflammatory cells, in cardiovascular diseases. We speculated that a specific CXCR4 ligand, [⁶⁸Ga]pentixafor, along with novel techniques for motion correction, would facilitate the in vivo characterization of CXCR4 expression in small culprit and nonculprit coronary atherosclerotic lesions after acute myocardial infarction by motion-corrected targeted PET/CT.

Methods

CXCR4 expression was analysed ex vivo in separately obtained arterial wall specimens. [⁶⁸Ga]Pentixafor PET/CT was performed in 37 patients after stent-based reperfusion for a first acute ST-segment elevation myocardial infarction. List-mode PET data were reconstructed to five different datasets using cardiac and/or respiratory gating. Guided by CT for localization, the PET signals of culprit and various groups of nonculprit coronary lesions were analysed and compared.

Results

Ex vivo, CXCR4 was upregulated in atherosclerotic lesions, and mainly colocalized with CD68⁺ inflammatory cells. In vivo, elevated CXCR4 expression was detected in culprit and nonculprit lesions, and the strongest CXCR4 PET signal (median SUV_max 1.96; interquartile range, IQR, 1.55–2.31) was observed in culprit coronary artery lesions. Stented nonculprit lesions (median SUV_max 1.45, IQR 1.23–1.88; P = 0.048) and hot spots in naive remote coronary segments (median SUV_max 1.34, IQR 1.23–1.74; P = 0.0005) showed significantly lower levels of CXCR4 expression. Dual cardiac/respiratory gating provided the strongest CXCR4 PET signal and the highest lesion detectability.

Conclusion

We demonstrated the basic feasibility of motion-corrected targeted PET/CT imaging of CXCR4 expression in coronary artery lesions, which was triggered by vessel wall inflammation but also by stent-induced injury. This novel methodology may serve as a platform for future diagnostic and therapeutic clinical studies targeting the biology of coronary atherosclerotic plaque.

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Title: Imaging of chemokine receptor CXCR4 expression in culprit and nonculprit coronary atherosclerotic plaque using motion-corrected [68Ga]pentixafor PET/CT
Authors: Thorsten Derlin
Daniel G. Sedding
Jochen Dutzmann
Arash Haghikia
Tobias König
L. Christian Napp
Christian Schütze
Nicole Owsianski-Hille
Hans-Jürgen Wester
Saskia Kropf
James T. Thackeray
Jens P. Bankstahl
Lilli Geworski
Tobias L. Ross
Johann Bauersachs
Frank M. Bengel
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 11/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-018-4076-2

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