PET Study of S1PR1 Expression in Rodent Model of Myocardial Infarction.

IF 2.5 4区医学 Q2 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

Molecular Imaging and Biology Pub Date : 2025-08-06 DOI:10.1007/s11307-025-02039-8

Hong Chen, Lin Qiu, Hao Jiang, Wenjuan Zhou, Anil Kumar Soda, Attila Kovacs, Carla J Weinheimer, Robert J Gropler, Zhude Tu

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引用次数: 0

Abstract

Purpose: Acute myocardial infarction (MI) is a leading cause of morbidity and mortality worldwide. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator influencing numerous physiological processes. S1PR1 is the predominant isoform of the S1P receptor in cardiomyocytes and vascular endothelial cells. S1PR1 plays a critical role in preventing adverse cardiac remodeling. The importance of S1PR1 in cardiac physiology has led to the development of novel treatments for MI, including S1PR1 gene delivery strategies aimed at preventing heart failure. Monitoring the dynamic changes of S1PR1 post-MI is clinically significant for assessing cardiac remodeling. This study validated the ability of specific S1PR1 PET radiotracer [¹⁸F]FS1P1 to track changes in this signaling pathway, thereby providing a non-invasive diagnostic tool to quantify S1PR1 expression for investigating MI in vivo.

Procedures: We characterized the S1PR1 radiotracer [¹⁸F]FS1P1 in an echo-guided mouse model of MI. [¹⁸F]FDG PET was used to delineate the infarct area. Masson trichrome staining was used to identify cardiac fibrosis. Immunofluorescence (IF) experiment was conducted to demonstrate changes in S1PR1 expression after MI. Autoradiography was performed to evaluate the distribution of [¹⁸F]FS1P1 in MI heart tissues. MI (n = 4) and sham (n = 4) mice were scanned with [¹⁸F]FS1P1 PET at 2 days and 2 weeks post-MI, radioactivity uptake in the myocardium was calculated as the percentage of the injected dose per gram (%ID/g).

Results: The uptake of [¹⁸F]FS1P1 was significantly decreased by 31.8% in the infarct region at 2 days post-MI compared to the sham group (1.3 ± 0.3 vs. 1.9 ± 0.3), and decreased by 37.6% at 2 weeks post-MI (1.2 ± 0.5). Additionally, [¹⁸F]FS1P1 signal decreased by 20.8% in the non-infarct remote area at 2 weeks post-MI compared with the sham control (1.6 ± 0.4 vs. 2.0 ± 0.2). Autoradiography study confirmed the trend of decreased [¹⁸F]FS1P1 uptake in the MI tissues. IF studies confirmed that the change in the [¹⁸F]FS1P1 PET signal corresponded with the change in S1PR1 expression.

Conclusions: This study demonstrated the downregulation of S1PR1 expression following MI and validated the use of [¹⁸F]FS1P1 PET imaging as an effective tool for detecting changes in S1PR1 expression post-MI.

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鼠心肌梗死模型中S1PR1表达的PET研究。

目的：急性心肌梗死（MI）是世界范围内发病率和死亡率的主要原因。鞘氨醇-1-磷酸（S1P）是一种生物活性脂质介质，影响许多生理过程。S1PR1是心肌细胞和血管内皮细胞中S1P受体的主要亚型。S1PR1在预防不良心脏重构中起关键作用。S1PR1在心脏生理学中的重要性导致了心肌梗死新治疗方法的发展，包括旨在预防心力衰竭的S1PR1基因传递策略。监测心肌梗死后S1PR1的动态变化对评估心肌重构具有重要的临床意义。本研究验证了特异性S1PR1 PET示踪剂[18F]FS1P1追踪该信号通路变化的能力，从而为体内研究心肌梗死提供了一种量化S1PR1表达的非侵入性诊断工具。方法：我们在超声引导的心肌梗死小鼠模型中表征了S1PR1放射性示踪剂[18F]FS1P1。[18F]FDG PET描绘梗死区域。马松三色染色法检测心肌纤维化。采用免疫荧光法（IF）观察心肌梗死后S1PR1表达的变化，采用放射自显影法评估[18F]FS1P1在心肌梗死心脏组织中的分布。心肌梗死（n = 4）和假手术（n = 4）小鼠分别于心肌梗死后第2天和第2周用[18F]FS1P1 PET扫描，以每克注射剂量的百分比（%ID/g）计算心肌放射性摄取。结果：心肌梗死后2天梗死区[18F]FS1P1摄取比假手术组显著降低31.8%(1.3±0.3∶1.9±0.3)，心肌梗死后2周[18F]FS1P1摄取比假手术组显著降低37.6%（1.2±0.5）。此外，在心肌梗死后2周，[18F]非梗死区FS1P1信号比假对照组下降20.8%（1.6±0.4比2.0±0.2）。放射自显像研究证实了心肌梗死组织中FS1P1摄取[18F]减少的趋势。IF研究证实[18F]FS1P1 PET信号的变化与S1PR1表达的变化相对应。结论：本研究证实心肌梗死后S1PR1表达下调，并验证了[18F]FS1P1 PET成像作为检测心肌梗死后S1PR1表达变化的有效工具。

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来源期刊

Molecular Imaging and Biology 医学-核医学

CiteScore

6.90

自引率

3.20%

发文量

审稿时长

3 months

期刊介绍： Molecular Imaging and Biology (MIB) invites original contributions (research articles, review articles, commentaries, etc.) on the utilization of molecular imaging (i.e., nuclear imaging, optical imaging, autoradiography and pathology, MRI, MPI, ultrasound imaging, radiomics/genomics etc.) to investigate questions related to biology and health. The objective of MIB is to provide a forum to the discovery of molecular mechanisms of disease through the use of imaging techniques. We aim to investigate the biological nature of disease in patients and establish new molecular imaging diagnostic and therapy procedures. Some areas that are covered are: Preclinical and clinical imaging of macromolecular targets (e.g., genes, receptors, enzymes) involved in significant biological processes. The design, characterization, and study of new molecular imaging probes and contrast agents for the functional interrogation of macromolecular targets. Development and evaluation of imaging systems including instrumentation, image reconstruction algorithms, image analysis, and display. Development of molecular assay approaches leading to quantification of the biological information obtained in molecular imaging. Study of in vivo animal models of disease for the development of new molecular diagnostics and therapeutics. Extension of in vitro and in vivo discoveries using disease models, into well designed clinical research investigations. Clinical molecular imaging involving clinical investigations, clinical trials and medical management or cost-effectiveness studies.