Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging
A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68 Ga-labeled GLP-1 (7-37) peptides in...
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| Language: | English |
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SAGE Publishing
2015-01-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2014.00057 |
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| author | Babak Behnam Azad Vanessa Rota Lihai Yu Rebecca Mcgirr André H. St. Amant Ting-Yim Lee Savita Dhanvantari Leonard G. Luyt PhD |
| author_facet | Babak Behnam Azad Vanessa Rota Lihai Yu Rebecca Mcgirr André H. St. Amant Ting-Yim Lee Savita Dhanvantari Leonard G. Luyt PhD |
| author_sort | Babak Behnam Azad |
| collection | DOAJ |
| description | A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68 Ga-labeled GLP-1 (7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression. |
| format | Article |
| id | doaj-art-5f3b5e72033541fca3b13a2fb36b1292 |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-5f3b5e72033541fca3b13a2fb36b12922025-01-02T22:37:58ZengSAGE PublishingMolecular Imaging1536-01212015-01-011410.2310/7290.2014.00057Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R ImagingBabak Behnam Azad0Vanessa Rota1Lihai Yu2Rebecca Mcgirr3André H. St. Amant4Ting-Yim Lee5Savita Dhanvantari6Leonard G. Luyt PhD7Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.Departments of Chemistry, Medical Biophysics, Medicine, Pathology, Medical Imaging, Oncology, The University of Western Ontario; Lawson Health Research Institute; London Regional Cancer Program, London, ON.A fluorescein-GLP-1 (7-37) analog was generated to determine GLP-1R distribution in various cell types of the pancreas in both strains of mice and receptor-specific uptake was confirmed by blocking with exendin-4. Biodistribution studies were carried out using 68 Ga-labeled GLP-1 (7-37) peptides in CD1 and C57BL/6 mice. In addition, immunocompromised mice bearing GLP-1R-expressing insulinomas were evaluated by positron emission tomography (PET) imaging and ex vivo biodistribution studies. The optical GLP-1 probe strongly colocalized with immunofluorescence for insulin and glucagon, and more weakly with amylase (exocrine pancreas) and cytokeratin 19 (ductal cells), confirming its application for in situ GLP-1R imaging in various pancreatic cell types. Insulinomas were clearly visualized by in vivo PET. Reducing the peptide positive charge decreased renal retention as well as tumor uptake. Results demonstrate the application of the developed GLP-1 peptide analogues for in situ (optical) and in vivo (PET) imaging of GLP-1R expression.https://doi.org/10.2310/7290.2014.00057 |
| spellingShingle | Babak Behnam Azad Vanessa Rota Lihai Yu Rebecca Mcgirr André H. St. Amant Ting-Yim Lee Savita Dhanvantari Leonard G. Luyt PhD Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging Molecular Imaging |
| title | Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging |
| title_full | Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging |
| title_fullStr | Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging |
| title_full_unstemmed | Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging |
| title_short | Synthesis and Evaluation of Optical and PET GLP-1 Peptide Analogues for GLP-1R Imaging |
| title_sort | synthesis and evaluation of optical and pet glp 1 peptide analogues for glp 1r imaging |
| url | https://doi.org/10.2310/7290.2014.00057 |
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