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.

中文翻译：

---

用于成像心脏生长激素促分泌素受体的18F标记的Ghrelin拟肽的开发和表征。

三分之一的心脏病患者会发展为心力衰竭，可通过对循环生物标志物进行成像和检测来诊断。成像策略揭示了形态和功能的变化，但未能检测到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。与生长激素释放激素结合的心脏生长激素促分泌素受体1a（GHSR1a）是心力衰竭的潜在生物标志物。我们已经合成和表征了新型ghrelin拟肽示踪剂，一种G-7039的18F标记类似物，用于心脏GHSR1a的正电子发射断层扫描（PET）成像。体外分析显示，与天然生长素释放肽相比，血清稳定性增强，并且表达GHSR1a的OVCAR细胞的细胞摄取显着增加。在小鼠中进行的生物分布研究表明，示踪剂的组织吸收与循环生长素释放肽水平无关，并且肝脏，肠和肾的心脏吸收和高吸收都可以忽略不计。使用ghsr-/-小鼠评估示踪剂摄取的特异性。静态和动态PET成像均显示心脏摄取无差异，心脏标准化摄取值与GHSR1a表达之间无显着相关性。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。在小鼠中进行的生物分布研究表明，示踪剂的组织吸收与循环生长素释放肽水平无关，并且肝脏，肠和肾的心脏吸收和高吸收都可以忽略不计。使用ghsr-/-小鼠评估示踪剂摄取的特异性。静态和动态PET成像均显示心脏摄取无差异，心脏标准化摄取值与GHSR1a表达之间无显着相关性。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。在小鼠中进行的生物分布研究表明，示踪剂的组织吸收与循环生长素释放肽水平无关，并且肝脏，肠和肾的心脏吸收和高吸收都可以忽略不计。使用ghsr-/-小鼠评估示踪剂摄取的特异性。静态和动态PET成像均显示心脏摄取无差异，心脏标准化摄取值与GHSR1a表达之间无显着相关性。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。心脏标准化摄取值与GHSR1a表达之间无显着相关性。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。心脏标准化摄取值与GHSR1a表达之间无显着相关性。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。