Development and Characterization of an 18F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor.

IF 2.2 4区 医学 Q3 BIOCHEMICAL RESEARCH METHODS
Ahmed Abbas, Lihai Yu, Tyler Lalonde, Derek Wu, Jonathan D Thiessen, Leonard G Luyt, Savita Dhanvantari
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引用次数: 4

Abstract

One-third of patients with heart disease develop heart failure, which is diagnosed through imaging and detection of circulating biomarkers. Imaging strategies reveal morphologic and functional changes but fall short of detecting molecular abnormalities that can lead to heart failure, and circulating biomarkers are not cardiac specific. Thus, there is critical need for biomarkers that are endogenous to myocardial tissues. The cardiac growth hormone secretagogue receptor 1a (GHSR1a), which binds the hormone ghrelin, is a potential biomarker for heart failure. We have synthesized and characterized a novel ghrelin peptidomimetic tracer, an 18F-labeled analogue of G-7039, for positron emission tomography (PET) imaging of cardiac GHSR1a. In vitro analysis showed enhanced serum stability compared to natural ghrelin and significantly increased cellular uptake in GHSR1a-expressing OVCAR cells. Biodistribution studies in mice showed that tissue uptake of the tracer was independent of circulating ghrelin levels, and there was negligible cardiac uptake and high uptake in the liver, intestines, and kidneys. Specificity of tracer uptake was assessed using ghsr -/- mice; both static and dynamic PET imaging revealed no difference in cardiac uptake, and there was no significant correlation between cardiac standardized uptake values and GHSR1a expression. Our study lays the groundwork for further refinement of peptidomimetic PET tracers targeting cardiac GHSR1a.

Abstract Image

Abstract Image

Abstract Image

用于心脏生长激素促分泌受体成像的18f标记胃饥饿素拟肽的研制和表征。
三分之一的心脏病患者会发生心力衰竭,这是通过成像和检测循环生物标志物来诊断的。成像策略显示形态和功能变化,但无法检测可能导致心力衰竭的分子异常,并且循环生物标志物不是心脏特异性的。因此,迫切需要心肌组织内源性的生物标志物。心脏生长激素促分泌素受体1a (GHSR1a)结合激素ghrelin,是心力衰竭的潜在生物标志物。我们已经合成并表征了一种新的ghrelin肽模拟示踪剂,一种18f标记的G-7039类似物,用于心脏GHSR1a的正电子发射断层扫描(PET)成像。体外分析显示,与天然胃饥饿素相比,其血清稳定性增强,表达ghsr1a的OVCAR细胞的细胞摄取显著增加。小鼠的生物分布研究表明,示踪剂的组织摄取与循环胃饥饿素水平无关,心脏摄取可以忽略不计,而肝脏、肠道和肾脏的摄取很高。用ghsr -/-小鼠评估示踪剂摄取的特异性;静态和动态PET成像显示心脏摄取无差异,心脏标准化摄取值与GHSR1a表达无显著相关性。我们的研究为进一步完善针对心脏GHSR1a的拟肽PET示踪剂奠定了基础。
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来源期刊
Molecular Imaging
Molecular Imaging Biochemistry, Genetics and Molecular Biology-Biotechnology
自引率
3.60%
发文量
21
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.
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