Development and Characterization of an F-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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-11-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.1177/1536012118809587 |
| _version_ | 1826904959259508736 |
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| author | Ahmed Abbas MSc Lihai Yu PhD Tyler Lalonde BSc Derek Wu BSc Jonathan D. Thiessen PhD Leonard G. Luyt PhD Savita Dhanvantari PhD |
| author_facet | Ahmed Abbas MSc Lihai Yu PhD Tyler Lalonde BSc Derek Wu BSc Jonathan D. Thiessen PhD Leonard G. Luyt PhD Savita Dhanvantari PhD |
| author_sort | Ahmed Abbas MSc |
| collection | DOAJ |
| description | 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 18 F-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. |
| first_indexed | 2024-03-07T17:10:33Z |
| format | Article |
| id | doaj.art-347f82c48655400bafc3a69fbf90d32e |
| institution | Directory Open Access Journal |
| issn | 1536-0121 |
| language | English |
| last_indexed | 2025-02-17T08:20:31Z |
| publishDate | 2018-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj.art-347f82c48655400bafc3a69fbf90d32e2025-01-02T23:11:41ZengSAGE PublishingMolecular Imaging1536-01212018-11-011710.1177/1536012118809587Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue ReceptorAhmed Abbas MSc0Lihai Yu PhD1Tyler Lalonde BSc2Derek Wu BSc3Jonathan D. Thiessen PhD4Leonard G. Luyt PhD5Savita Dhanvantari PhD6 Department of Medical Biophysics, Western University, London, Ontario, Canada Department of Chemistry, Western University, London, Ontario, Canada Department of Chemistry, Western University, London, Ontario, Canada Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada Imaging Research, Lawson Health Research Institute, London, Ontario, Canada Department of oncology, Western University, London, Ontario, Canada Metabolism/Diabetes, Lawson Health Research Institute, London, Ontario, CanadaOne-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 18 F-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.https://doi.org/10.1177/1536012118809587 |
| spellingShingle | Ahmed Abbas MSc Lihai Yu PhD Tyler Lalonde BSc Derek Wu BSc Jonathan D. Thiessen PhD Leonard G. Luyt PhD Savita Dhanvantari PhD Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor Molecular Imaging |
| title | Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor |
| title_full | Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor |
| title_fullStr | Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor |
| title_full_unstemmed | Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor |
| title_short | Development and Characterization of an F-labeled Ghrelin Peptidomimetic for Imaging the Cardiac Growth Hormone Secretagogue Receptor |
| title_sort | development and characterization of an f labeled ghrelin peptidomimetic for imaging the cardiac growth hormone secretagogue receptor |
| url | https://doi.org/10.1177/1536012118809587 |
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