Development and Characterization of an 18F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor.
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.
['Abbas|Ahmed|A|0000-0001-5107-5924', 'Yu|Lihai|L|', 'Lalonde|Tyler|T|', 'Wu|Derek|D|', 'Thiessen|Jonathan D|JD|', 'Luyt|Leonard G|LG|', 'Dhanvantari|Savita|S|0000-0001-6453-1386']
D000818:Animals D015415:Biomarkers D045744:Cell Line, Tumor D005215:Fasting D005247:Feeding Behavior D005260:Female D005462:Fluorine Radioisotopes D054439:Ghrelin D005934:Glucagon D052216:Glucagon-Like Peptide 1 D006801:Humans D007328:Insulin D008810:Mice, Inbred C57BL D009206:Myocardium D057786:Peptidomimetics D000072078:Positron Emission Tomography Computed Tomography D054440:Receptors, Ghrelin D013997:Time Factors D014018:Tissue Distribution
ghrelin imaging cardiac heart disease heart failure biomarkers GHSR1a PET