[68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques

Abstract

Purpose: The expression of chemokine receptor type 4 (CXCR4) was found co-localized with macrophages on the atherosclerotic vessel wall and participated in the initial emigration of leukocytes. Gallium-68 [⁶⁸Ga]Pentixafor has recently been introduced for the imaging of atherosclerosis by targeting CXCR4. We sought to evaluate human atherosclerotic lesions using [⁶⁸Ga]Pentixafor PET/MRI.

Methods: Thirty-eight oncology patients underwent [⁶⁸Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUV_max) were derived from hot lesions in seven arterial segments and target-to-blood ratios (TBR) were calculated. ANOVA post-hoc and paired t test were performed for statistical comparison, Spearman's correlation coefficient between uptake ratios and cardiovascular risk factors were assessed. The reproducibility of [⁶⁸Ga]Pentixafor PET/MRI was assessed in seven patients with a follow-up exanimation by Pearson's regression and Bland-Altman plots analysis.

Results: Thirty-four of 38 patients showed 611 focal [⁶⁸Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBR_max were highest in the descending aorta. There were significantly higher TBR values found in men (1.9 ± 0.3) as compared to women (1.7 ± 0.2; p < 0.05). Patients with mean TBR_max > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBR_max ≤ 1.7. [⁶⁸Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBR_max values of plaque lesions (TBR_baseline1.8 ± 0.3 vs TBR_follow-up1.8 ± 0.3) (p = 0.9).

Conclusion: Patients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [⁶⁸Ga]Pentixafor in characterization of atherosclerosis.

Keywords: Atherosclerosis; Chemokine receptor type 4; PET/MRI; [68Ga]Pentixafor.

Fig. 1

Representative axial slices of [⁶⁸Ga]Pentixafor TOF-PET of the right carotid artery in a 71-year-old male lymphoma patient. Increased focal [⁶⁸Ga]Pentixafor Uptake was detected at a carotid artery stenosis (arrow)

Fig. 2

Reproducibility of [⁶⁸Ga]Pentixafor PET imaging in atherosclerotic plaques from a representative scan of a 76-year-old female lymphoma patient. Co-localized uptake in both baseline and follow-up scans was observed (time interval = four months). Transverse view of PET/MRI scan showed spatial accumulation of [⁶⁸Ga]Pentixafor within the mixed atherosclerotic lesions in the descending aortas

Fig. 3

CXCR4 expression in a representative inflamed carotid plaque lesion. Brightfield micrographs showed brown chemoimmunoreactive CXCR4 and CD68 (macrophage) staining. Co-localized CXCR4 and CD68 expression was observed in these two adjacent sections

Fig. 4

a Incidence of major cardiovascular risk factors and b Medications proportion in according to a mean TBRmax cut-off value of 1.7. CAD: cardiovascular diseases, BMI: body-mass index. ACE: Angiotensin-converting-enzyme

Fig. 5

a, Pearson linear regression analysis (r = 0.6, p < 0.01) between TBRmax at baseline scans and TBRmax at follow-up scans. b, Bland Altman analysis of the agreement of maximum TBR within atherosclerotic lesions between baseline and follow-up, with a lower bias of −0.03 for the mean TBRmax