左心室重构与急性心肌梗死后远程心肌一过性[Ga]Ga-戊聚糖素活性升高相关。

Left Ventricular Remodelling Associated with the Transient Elevated [Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.

机构信息

Department of Nuclear Medicine, First Hospital of Shanxi Medical University, No. 85 Jiefang South Road, Taiyuan, 030001, Shanxi, China.

Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Shanxi Medical University, Taiyuan, China.

出版信息

Mol Imaging Biol. 2024 Aug;26(4):693-703. doi: 10.1007/s11307-024-01912-2. Epub 2024 Apr 19.

DOI:10.1007/s11307-024-01912-2

PMID:38641708

Abstract

BACKGROUND

Previous studies have initially reported accompanying elevated 2-deoxy-2[F]fluoro-D-glucose ([F]F-FDG) inflammatory activity 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. [Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function.

METHODS

Twelve AMI rats and six Sham rats serially underwent [Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively.

RESULTS

The uptake of [Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), 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 activity in the infarct territory, [Ga]Ga-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 activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05).

CONCLUSIONS

Corresponding with the peaked [Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential.

摘要

背景

先前的研究初步报告了急性心肌梗死（AMI）后，远隔区域伴随的 2-脱氧-2[F]氟-D-葡萄糖（[F]F-FDG）炎症活性升高及其预后价值。对远隔心肌伴随炎症的非侵入性特征分析可能对指导未来的靶向治疗具有潜力。[Ga]Ga-戊聚糖靶向炎症细胞表面的趋化因子受体 4（CXCR4），是目前很有前途的炎症成像剂之一。在这项研究中，我们旨在关注 AMI 后远隔心肌中[Ga]Ga-戊聚糖活性的纵向演变及其与心功能的关系。

方法

12 只 AMI 大鼠和 6 只假手术大鼠分别在术前、术后 5、7、14 天进行[Ga]Ga-戊聚糖成像。评估最大和平均标准摄取值（SUV）和靶与背景比（TBR）以指示摄取强度。进行门控[F]F-FDG 成像和免疫荧光染色，分别获得心功能和促炎和修复性巨噬细胞的反应。

结果

梗塞心肌中[Ga]Ga-戊聚糖的摄取在第 5 天达到峰值（均 P=0.003），在第 7 天保持不变（均 P=0.011），在 AMI 后第 14 天恢复（P>0.05），与上升下降的促炎 M1 巨噬细胞一致（P<0.05）。与梗塞部位的峰值活性相关，AMI 后早期（第 5 天）远隔心肌中[Ga]Ga-戊聚糖的摄取显著增加（AMI 与 Sham：SUVmean、SUVmax 和 TBRmean：均 P<0.05），并与同期 EDV 和/或 ESV 强烈相关（SUVmean 和 TBRmean：均 P<0.05）。第 7 天 AMI 后，这种短暂的远隔活性恢复（AMI 与 Sham：P>0.05）。