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
{"title":"[18F]TZ-Z09591（一种靶向血小板衍生生长因子受体β的亲和分子）对肝脏纤维化的成像。","authors":"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","doi":"10.1186/s41181-023-00210-6","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>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 ([<sup>18</sup>F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis.</p><h3>Results</h3><p>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 [<sup>18</sup>F]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 [<sup>18</sup>F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars.</p><h3>Conclusions</h3><p>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.</p><h3>Graphical abstract</h3>\n <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\n </div>","PeriodicalId":534,"journal":{"name":"EJNMMI Radiopharmacy and Chemistry","volume":"8 1","pages":""},"PeriodicalIF":4.4000,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513984/pdf/","citationCount":"1","resultStr":"{\"title\":\"Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β\",\"authors\":\"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\",\"doi\":\"10.1186/s41181-023-00210-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>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 ([<sup>18</sup>F]TZ-Z09591) as a PET tracer for imaging liver fibrogenesis.</p><h3>Results</h3><p>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 [<sup>18</sup>F]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 [<sup>18</sup>F]TZ-Z09591 binding in the liver was increased in fibrotic livers (p = 0.02) and corresponded to binding in fibrotic scars.</p><h3>Conclusions</h3><p>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.</p><h3>Graphical abstract</h3>\\n <div><figure><div><div><picture><source><img></source></picture></div></div></figure></div>\\n </div>\",\"PeriodicalId\":534,\"journal\":{\"name\":\"EJNMMI Radiopharmacy and Chemistry\",\"volume\":\"8 1\",\"pages\":\"\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2023-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513984/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EJNMMI Radiopharmacy and Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://link.springer.com/article/10.1186/s41181-023-00210-6\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, INORGANIC & NUCLEAR\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EJNMMI Radiopharmacy and Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s41181-023-00210-6","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, INORGANIC & NUCLEAR","Score":null,"Total":0}
Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β
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.
![Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β](https://img.booksci.cn/booksciimg/2023-9/2023102378231631966292091511221.jpg)
![Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β](https://img.booksci.cn/booksciimg/2023-9/2023102378245052142703732990721.jpg)
![Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β](https://img.booksci.cn/booksciimg/2023-9/2023102378245828913895796737360.jpg)
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