Longitudinal evolution of 68 Ga-Pentixafor uptake in the remote myocardium early after acute myocardial infarction and its association with left ventricular remodelling

Abstract

Abstract Purpose Previous studies have initially reported accompanying elevated 18F-FDG inflammatory signal in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. In this study, we sought to focus on the longitudinal evolution of 68Ga-Pentixafor signals in the remote myocardium following AMI. Methods Twelve AMI rats and six Sham rats serially underwent 68Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target(myocardium)-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated 18F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively. Results The uptake of 68Ga-Pentixafor in the infarcted myocardium peaked on day 5 (P < 0.001), retained at day 7 (P < 0.01), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak signal in the infarct territory, 68Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote signal recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05). Conclusions Corresponding with the peaked 68Ga-Pentixafor signal in the infarct area, the signal in the remote region also elevated accordingly and led to left ventricular remodelling early after AMI, which was attributed to the early surge of pro-inflammatory response. Further studies are warranted in the remote myocardium to clarify the post-inflammation mechanism and the prognostic value.