학술논문
Imaging of fibrogenesis in the liver by [.sup.18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor [beta]
Research Article
Research Article
Document Type
Report
Author
Source
EJNMMI Radiopharmacy and Chemistry. December 2023, Vol. 8 Issue 1
Subject
Language
English
Abstract
Author(s): Olivia Wegrzyniak [sup.1] , Bo Zhang [sup.1] , Johanna Rokka [sup.2] , Maria Rosestedt [sup.1] , Bogdan Mitran [sup.1] [sup.3] , Pierre Cheung [sup.1] , Emmi Puuvuori [sup.1] , [...]
Background Platelet-derived growth factor receptor beta (PDGFR[beta]) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFR[beta] could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([.sup.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 PDGFR[beta]. Biodistribution performed on healthy rats showed rapid clearance of [.sup.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 [.sup.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
Background Platelet-derived growth factor receptor beta (PDGFR[beta]) is a receptor overexpressed on activated hepatic stellate cells (aHSCs). Positron emission tomography (PET) imaging of PDGFR[beta] could potentially allow the quantification of fibrogenesis in fibrotic livers. This study aims to evaluate a fluorine-18 radiolabeled Affibody molecule ([.sup.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 PDGFR[beta]. Biodistribution performed on healthy rats showed rapid clearance of [.sup.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 [.sup.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