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

Eur J Nucl Med Mol Imaging. 2019 Jul;46(8):1616-1625. doi: 10.1007/s00259-019-04322-7. Epub 2019 Apr 19.

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.

Keywords: Atherosclerosis; CXCR4; Carotid artery; PET/MRI; [68Ga]Pentixafor.

MeSH terms

  • Aged
  • Carotid Arteries / diagnostic imaging*
  • Carotid Arteries / metabolism
  • Carotid Artery Diseases / diagnostic imaging*
  • Carotid Artery Diseases / pathology
  • Coordination Complexes
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Middle Aged
  • Multimodal Imaging / methods*
  • Peptides, Cyclic
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*

Substances

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