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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-10

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

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 SUVmax 1.96; interquartile range, IQR, 1.55-2.31) was observed in culprit coronary artery lesions. Stented nonculprit lesions (median SUVmax 1.45, IQR 1.23-1.88; P = 0.048) and hot spots in naive remote coronary segments (median SUVmax 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. More... »

PAGES

1934-1944

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00259-018-4076-2

DOI

http://dx.doi.org/10.1007/s00259-018-4076-2

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105256894

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29967943


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