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

Eur J Nucl Med Mol Imaging. 2018 Oct;45(11):1934-1944. doi: 10.1007/s00259-018-4076-2. Epub 2018 Jul 3.

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.

Keywords: Atherosclerosis; CXCR4; Myocardial infarction; Plaque; Positron emission tomography.

MeSH terms

  • Aged
  • Coordination Complexes*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Movement*
  • Myocardial Infarction / complications
  • Peptides, Cyclic*
  • Plaque, Atherosclerotic / complications
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / metabolism*
  • Plaque, Atherosclerotic / physiopathology
  • Positron Emission Tomography Computed Tomography*
  • Receptors, CXCR4 / metabolism*
  • Respiration
  • Retrospective Studies

Substances

  • 68Ga-pentixafor
  • Coordination Complexes
  • Peptides, Cyclic
  • Receptors, CXCR4