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

被引：4

作者：

Abbas, Ahmed ^{[1
]}

Yu, Lihai ^{[2
]}

Lalonde, Tyler ^{[2
]}

Wu, Derek ^{[3
]}

Thiessen, Jonathan D. ^{[1
,4
]}

Luyt, Leonard G. ^{[2
,4
,5
]}

Dhanvantari, Savita ^{[1
,3
,4
,6
]}

机构：

[1] Western Univ, Dept Med Biophys, London, ON, Canada

[2] Western Univ, Dept Chem, London, ON, Canada

[3] Western Univ, Dept Pathol & Lab Med, London, ON, Canada

[4] Lawson Hlth Res Inst, Imaging Res, London, ON, Canada

[5] Western Univ, Dept Oncol, London, ON, Canada

[6] Lawson Hlth Res Inst, Metab Diabet, London, ON, Canada

来源：

MOLECULAR IMAGING | 2018年 / 17卷

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

ghrelin; GHSR1a; cardiac; imaging; PET; biomarkers; heart failure; heart disease; FLUORINE; DESIGN; IDENTIFICATION; PROGLUCAGON; TISSUE; ANALOG; CELLS;

D O I：

10.1177/1536012118809587

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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 F-18-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.

引用

页数：11