Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β
Abstract Background Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to ev...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2023-09-01
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| Series: | EJNMMI Radiopharmacy and Chemistry |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s41181-023-00210-6 |
| _version_ | 1797555610532708352 |
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| author | Olivia Wegrzyniak Bo Zhang Johanna Rokka Maria Rosestedt Bogdan Mitran Pierre Cheung Emmi Puuvuori Sofie Ingvast Jonas Persson Helena Nordström John Löfblom Fredrik Pontén Fredrik Y. Frejd Olle Korsgren Jonas Eriksson Olof Eriksson |
| author_facet | Olivia Wegrzyniak Bo Zhang Johanna Rokka Maria Rosestedt Bogdan Mitran Pierre Cheung Emmi Puuvuori Sofie Ingvast Jonas Persson Helena Nordström John Löfblom Fredrik Pontén Fredrik Y. Frejd Olle Korsgren Jonas Eriksson Olof Eriksson |
| author_sort | Olivia Wegrzyniak |
| collection | DOAJ |
| description | Abstract Background Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([18F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis. Results In vitro specificity studies demonstrated that the trans-Cyclooctenes (TCO) conjugated Z09591 Affibody molecule had a picomolar affinity for human PDGFRβ. Biodistribution performed on healthy rats showed rapid clearance of [18F]TZ-Z09591 through the kidneys and low liver background uptake. Autoradiography (ARG) studies on fibrotic livers from mice or humans correlated with histopathology results. Ex vivo biodistribution and ARG revealed that [18F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars. Conclusions Our study highlights [18F]TZ-Z09591 as a specific tracer for fibrogenic cells in the fibrotic liver, thus offering the potential to assess fibrogenesis clearly. Graphical abstract |
| first_indexed | 2024-03-10T16:49:55Z |
| format | Article |
| id | doaj.art-84daea9b1f234c4eacb9912e8eedc172 |
| institution | Directory Open Access Journal |
| issn | 2365-421X |
| language | English |
| last_indexed | 2024-03-10T16:49:55Z |
| publishDate | 2023-09-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | EJNMMI Radiopharmacy and Chemistry |
| spelling | doaj.art-84daea9b1f234c4eacb9912e8eedc1722023-11-20T11:21:12ZengSpringerOpenEJNMMI Radiopharmacy and Chemistry2365-421X2023-09-018111810.1186/s41181-023-00210-6Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor βOlivia Wegrzyniak0Bo Zhang1Johanna Rokka2Maria Rosestedt3Bogdan Mitran4Pierre Cheung5Emmi Puuvuori6Sofie Ingvast7Jonas Persson8Helena Nordström9John Löfblom10Fredrik Pontén11Fredrik Y. Frejd12Olle Korsgren13Jonas Eriksson14Olof Eriksson15Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Drug Discovery and Development Platform, Department of Chemistry-BMC, Uppsala UniversityDepartment of Protein Science, Division of Protein Engineering, KTH Royal Institute of TechnologyDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityDepartment of Immunology, Genetics and Pathology, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala UniversityAbstract Background Platelet-derived growth factor receptor beta (PDGFRβ) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFRβ could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([18F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis. Results In vitro specificity studies demonstrated that the trans-Cyclooctenes (TCO) conjugated Z09591 Affibody molecule had a picomolar affinity for human PDGFRβ. Biodistribution performed on healthy rats showed rapid clearance of [18F]TZ-Z09591 through the kidneys and low liver background uptake. Autoradiography (ARG) studies on fibrotic livers from mice or humans correlated with histopathology results. Ex vivo biodistribution and ARG revealed that [18F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars. Conclusions Our study highlights [18F]TZ-Z09591 as a specific tracer for fibrogenic cells in the fibrotic liver, thus offering the potential to assess fibrogenesis clearly. Graphical abstracthttps://doi.org/10.1186/s41181-023-00210-6PET imagingPlatelet derived growth factor receptorHepatic stellate cellsFibrogenesisLiver fibrosis |
| spellingShingle | Olivia Wegrzyniak Bo Zhang Johanna Rokka Maria Rosestedt Bogdan Mitran Pierre Cheung Emmi Puuvuori Sofie Ingvast Jonas Persson Helena Nordström John Löfblom Fredrik Pontén Fredrik Y. Frejd Olle Korsgren Jonas Eriksson Olof Eriksson Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β EJNMMI Radiopharmacy and Chemistry PET imaging Platelet derived growth factor receptor Hepatic stellate cells Fibrogenesis Liver fibrosis |
| title | Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β |
| title_full | Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β |
| title_fullStr | Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β |
| title_full_unstemmed | Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β |
| title_short | Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β |
| title_sort | imaging of fibrogenesis in the liver by 18f tz z09591 an affibody molecule targeting platelet derived growth factor receptor β |
| topic | PET imaging Platelet derived growth factor receptor Hepatic stellate cells Fibrogenesis Liver fibrosis |
| url | https://doi.org/10.1186/s41181-023-00210-6 |
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