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

Abstract

PurposeThe 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.MethodsCXCR4 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.ResultsEx 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.ConclusionWe 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.Electronic supplementary materialThe online version of this article (10.1007/s00259-018-4076-2) contains supplementary material, which is available to authorized users.

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

“…Hyafil et al reported from a preclinical study that the CXCR4 protein was expressed in macrophage-rich arterial tissues, and demonstrated great potential for [ 68 Ga]Pentixafor PET to specifically recognize inflamed atherosclerotic lesions [ 18 ]. In another recent study, Derlin et al demonstrated that the [ 68 Ga]Pentixafor PET signal intensively accumulated in culprit coronary atherosclerotic plaques of patients with recent acute myocardial infarction [ 19 ].…”

“…Thus, [ 68 Ga]Pentixafor demonstrated its potential for atherosclerotic plaque imaging not only because the CXCR4 protein is expressed at various cell types related to atherogenesis [ 12 , 30 – 34 ] and particularly the intensive co-localization of CXCR4 expression and macrophages ensures an adequate radio-signal for PET imaging, but also importantly, compared to 18 F-FDG, low myocardial uptake of 68 Ga-pentixfor could enable coronary imaging without specific patient preparation [ 19 ].…”

“…Recently, [ 68 Ga]Pentixafor has been introduced as a novel PET tracer that specifically binds to the CXCR4 [ 16 ]. Moreover, [ 68 Ga]Pentixafor PET has been shown to be sensitive and reproducible for the characterization of atherosclerotic lesions [ 17 – 19 ]. Nevertheless, systematic quantification of the vascular uptake of [ 68 Ga]Pentixafor in atherosclerotic lesions still requires an accurate delineation of plaques.…”

CXCR4-binding PET tracers link monocyte recruitment and endothelial injury in murine atherosclerosis

“…To further investigate the hypothesis that CXCR4 signal reports the level of endothelial injury in atherosclerosis, we compared 64 Cu-DOTA-vMIP-II to 64 Cu-DOTA-FC131, a CXCR4 specific tracer. Although PET signals arising from CXCR4-specific tracer is already reported in atherosclerosis (41)(42)(43)(44), the plaque characteristics, or biological parameters of plaque activity, that may or may not correlate with its PET signal are still not fully understood. Similar to studies with the vMIP-II tracer ( Fig.…”

The clinical utility of hybrid imaging for the identification of vulnerable plaque and vulnerable patients

“…11C-PK11195 is able to image intraplaque haemorrhage in recently symptomatic carotid plaques 44 as well as active disease in large-vessel vasculitis, while CXCR4 has recently shown promise for the distinguising culprit and non-culprit coronary plaques in ST-elevation myocardial infarction. 45…”