Positron Emission Tomography (PET) with 18F-FGA for Diagnosis of Myocardial Infarction in a Coronary Artery Ligation Model

IF 2.8 4区医学 Q2 Medicine

Molecular Imaging Pub Date : 2022-02-09 DOI:10.1155/2022/9147379

V. Awasthi, H. Gali, A. Hedrick, Huining Da, Venkateswararao Eeda, D. Jain

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引用次数: 1

Abstract

Location and extent of necrosis are valuable information in the management of myocardial infarction (MI). Methods. We investigated 2-deoxy-2-18F-fluoro glucaric acid (FGA), a novel infarct-avid agent, for positron emission tomography (PET) of MI. We synthesized FGA from commercially available 18F-fluoro-2-deoxy-2-D-glucose (FDG). MI was induced in mice by permanently occluding the left anterior descending coronary artery. Biodistribution of FGA was assessed 1 h after FGA injection (11 MBq). PET/CT was conducted 1 h, 6 h, 1 d, 3 d, and 4 d after MI. Subcellular compartment of FGA accumulation in necrosis was studied by tracing the uptake of biotin-labeled glucaric acid with streptavidin-HRP in H2O2-treated H9c2 cardiomyoblasts. Streptavidin-reactive protein bands were identified by LC-MS/MS. Results. We obtained a quantitative yield of FGA from FDG within 7 min (radiochemical purity > 99%). Cardiac uptake of FGA was significantly higher in MI mice than that in control mice. Imaging after 1 h of FGA injection delineated MI for 3 days after MI induction, with negligible background signal from surrounding tissues. Myocardial injury was verified by tetrazolium staining and plasma troponin (47.63 pg/mL control versus 311.77 pg/mL MI). In necrotic H9c2 myoblasts, biotinylated glucaric acid accumulated in nuclear fraction. LC-MS/MS primarily identified fibronectin in necrotic cells as a putative high fidelity target of glucaric acid. Conclusion. FGA/PET detects infarct early after onset of MI and FGA accumulation in infarct persists for 3 days. Its retention in necrotic cells appears to be a result of interaction with fibronectin that is known to accumulate in injured cardiac tissue.

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正电子发射断层扫描(PET)与18F-FGA诊断冠状动脉结扎模型心肌梗死

坏死的位置和程度是心肌梗死(MI)治疗中有价值的信息。方法。我们研究了一种新型梗死药物-2-脱氧-2- 18f -氟葡萄糖酸(FGA)，用于心肌梗死的正电子发射断层扫描(PET)。我们从市售的18f -氟-2-脱氧-2-d -葡萄糖(FDG)合成了FGA。永久性阻断小鼠左冠状动脉前降支诱导心肌梗死。注射FGA (11 MBq) 1 h后测定FGA的生物分布。在心肌梗死后1小时、6小时、1天、3天、4天进行PET/CT扫描。用链亲和素hrp追踪h2o2处理的H9c2心肌细胞对生物素标记的葡萄糖酸的摄取，研究坏死细胞中FGA积累的亚细胞区室。采用LC-MS/MS鉴别链霉亲和素反应蛋白条带。结果。我们在7分钟内从FDG中获得了FGA的定量产率(放射化学纯度bb0 99%)。心肌梗死小鼠对FGA的心脏摄取明显高于对照组小鼠。注射FGA 1小时后的成像描绘了心肌梗死诱导后3天的心肌梗死，周围组织的背景信号可以忽略不计。通过四氮唑染色和血浆肌钙蛋白(对照组47.63 pg/mL，心肌梗死311.77 pg/mL)证实心肌损伤。在坏死的H9c2成肌细胞中，生物素化的葡萄糖酸在细胞核部分积累。LC-MS/MS主要鉴定坏死细胞中的纤维连接蛋白是葡萄糖酸的高保真靶标。结论。FGA/PET在心肌梗死发病后早期检测到梗死，FGA在梗死内的积累持续3天。它在坏死细胞中的滞留似乎是与纤维连接蛋白相互作用的结果，纤维连接蛋白已知在损伤的心脏组织中积累。

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来源期刊

Molecular Imaging 生物-核医学

CiteScore

4.50

自引率

3.60%

发文量

审稿时长

>12 weeks

期刊介绍： Molecular Imaging is a peer-reviewed, open access journal highlighting the breadth of molecular imaging research from basic science to preclinical studies to human applications. This serves both the scientific and clinical communities by disseminating novel results and concepts relevant to the biological study of normal and disease processes in both basic and translational studies ranging from mice to humans.