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

Abstract

PurposeThe 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.MethodsThirty-eight oncology patients underwent [68Ga]Pentixafor PET/MR imaging at baseline. Maximum standardized uptake values (SUVmax) 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.ResultsThirty-four of 38 patients showed 611 focal [68Ga]Pentixafor uptake that followed the contours of the large arteries. Both prevalence and mean TBRmax 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 TBRmax > 1.7 showed a significantly higher incidence of diabetes, hypertension hypercholesterolemia and history of cardiovascular disease than patients with mean TBRmax ≤ 1.7. [68Ga]Pentixafor uptake showed a good reproducibility (r = 0.6, p < 0.01), and there was no difference between the mean TBRmax values of plaque lesions (TBRbaseline1.8 ± 0.3 vs TBRfollow-up1.8 ± 0.3) (p = 0.9).ConclusionPatients with high arterial uptake showed increased incidence of cardiovascular risk factors, suggesting a potential role of [68Ga]Pentixafor in characterization of atherosclerosis.

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

“…Obviously, not all lesions observed on PET in vivo can be verified by histology (which applies to all clinical atherosclerosis studies). However, there are recent clinical studies evaluating the usefulness of pentixafor for CXCR4 imaging in plaque [ 14 , 38 ], and also studies which have demonstrated that the arterial wall uptake can be blocked, is specific, reproducible, and correlates with the presence of CXCR4 + cells [ 16 , 38 ]. In addition, the ex vivo data presented in this work confirm the presence of CXCR4 + cells in the coronary wall, and demonstrate an increasing number of these cells with advancing pathology of lesions, in line with the observed in vivo PET data.…”

Radionuclide imaging of inflammation in atherosclerotic vascular disease among people living with HIV infection: current practice and future perspective

“…In a larger human study of 38 patients, 611 foci of Ga-68 Pentixafor uptakes were seen in the vessels (Li et al 2017). The intensity of uptake correlated positively with the presence of CVD risk factors (male gender, diabetes, hypertension, hypercholesterolemia).…”

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.…”