Department of Nuclear Medicine, Hannover Medical School, Hannover, Germany.
Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany.
Theranostics. 2021 Jul 6;11(16):7984-7994. doi: 10.7150/thno.61423. eCollection 2021.
Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup. Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome. In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27). Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.
急性心肌梗死（MI）引发全身性炎症反应，包括心脏-肾脏轴的串扰。我们采用基于放射性核素的炎症靶向全身分子成像技术，在转化设置中识别 MI 后的潜在心脏-肾脏串扰。MI 后，对小鼠进行了连续的全身正电子发射断层扫描（PET），使用特异性 CXCR4 配体 Ga-Pentixafor。通过分析验证，比较肾脏和心脏与造血器官中的示踪剂保留，以评估全身性炎症，并与进行性收缩功能障碍相关。此外，96 名 MI 后一周内的患者接受了 Ga-Pentixafor PET，用于系统基础图像分析，并确定不良肾脏结局的预后价值。在小鼠中，MI 后早期短暂出现心肌 CXCR4 上调。心脏和肾脏 PET 信号在整个时间过程中直接相关（r = 0.62，p < 0.0001），表明器官之间存在炎症联系。放射性自显影（r = 0.9，p < 0.01）和 CD68 免疫染色表明信号定位于炎症细胞含量。MI 后 6 周时，7d 时的肾脏信号与左心室射血分数呈反比（r = -0.79，p < 0.01）。在患者中，肾脏 CXCR4 信号也与梗塞（r = 0.25，p < 0.05）和远程心肌（r = 0.39，p < 0.0001）的信号相关。在 96 名患者中有 48 名（50%）在随访期间有肾小球滤过率（GFR）。48 名中有 16 名（33.3%）在 MI 后平均 80.5 天肾功能恶化（GFR 损失> 5 毫升/分钟/1.73 米）。Kaplan-Meier 分析显示，远程心肌 CXCR4 信号升高的患者发生不良肾脏结局（p < 0.05）。多变量 Cox 分析证实了独立的预测价值（相对于基线 GFR、LVEF、梗塞面积；HR，5.27）。基于系统的 CXCR4 靶向分子成像技术可在 MI 后早期识别心脏-肾脏轴的炎症串扰。
