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采用代谢 ([F]FDG) 和灌注 (SYN1) 心脏存活示踪剂对心肌梗死后小动物模型进行多参数评估。

Multiparametric Evaluation of Post-MI Small Animal Models Using Metabolic ([F]FDG) and Perfusion-Based (SYN1) Heart Viability Tracers.

机构信息

Institute of Human Genetics, Polish Academy of Sciences, 60-479 Poznan, Poland.

Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warsaw, Poland.

出版信息

Int J Mol Sci. 2021 Nov 22;22(22):12591. doi: 10.3390/ijms222212591.

Abstract

Cardiovascular diseases (CVD), with myocardial infarction (MI) being one of the crucial components, wreak havoc in developed countries. Advanced imaging technologies are required to obtain quick and widely available diagnostic data. This paper describes a multimodal approach to in vivo perfusion imaging using the novel SYN1 tracer based on the fluorine-18 isotope. The NOD-SCID mice were injected intravenously with SYN1 or [F] fluorodeoxyglucose ([F]-FDG) radiotracers after induction of the MI. In all studies, the positron emission tomography-computed tomography (PET/CT) technique was used. To obtain hemodynamic data, mice were subjected to magnetic resonance imaging (MRI). Finally, the biodistribution of the SYN1 compound was performed using Wistar rat model. SYN1 showed normal accumulation in mouse and rat hearts, and MI hearts correctly indicated impaired cardiac segments when compared to [F]-FDG uptake. In vivo PET/CT and MRI studies showed statistical convergence in terms of the size of the necrotic zone and cardiac function. This was further supported with RNAseq molecular analyses to correlate the candidate function genes' expression, with , and , with and functional correlations showing statistical significance in both SYN1 and [F]-FDG. Our manuscript presents a new fluorine-18-based perfusion radiotracer for PET/CT imaging that may have importance in clinical applications. Future research should focus on confirmation of the data elucidated here to prepare SYN1 for first-in-human trials.

摘要

心血管疾病(CVD),其中心肌梗死(MI)是一个关键组成部分,在发达国家造成严重破坏。需要先进的成像技术来获取快速和广泛可用的诊断数据。本文描述了一种使用新型基于氟-18 同位素的 SYN1 示踪剂进行体内灌注成像的多模态方法。在 MI 诱导后,将 NOD-SCID 小鼠静脉内注射 SYN1 或 [F]氟脱氧葡萄糖 ([F]-FDG) 放射性示踪剂。在所有研究中,均使用正电子发射断层扫描-计算机断层扫描 (PET/CT) 技术。为了获得血流动力学数据,对小鼠进行磁共振成像 (MRI)。最后,使用 Wistar 大鼠模型进行 SYN1 化合物的生物分布研究。SYN1 在小鼠和大鼠心脏中表现出正常的积累,与 [F]-FDG 摄取相比,MI 心脏正确指示受损的心脏节段。体内 PET/CT 和 MRI 研究表明,坏死区大小和心脏功能方面具有统计学上的一致性。这进一步得到了 RNAseq 分子分析的支持,该分析将候选功能基因的表达与 、 和 进行了关联,并且 和 在 SYN1 和 [F]-FDG 中均显示出统计学意义上的功能相关性。我们的手稿介绍了一种用于 PET/CT 成像的新型基于氟-18 的灌注放射性示踪剂,它在临床应用中可能具有重要意义。未来的研究应集中在阐明这里的数据,以准备 SYN1 进行首次人体试验。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b89/8619497/69c489620c06/ijms-22-12591-g001.jpg

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