Imaging of fibrogenesis in the liver by [ 18 F]TZ-Z0959: an Affibody molecule targeting platelet derived growth factor receptor β

• Published in: EJNMMI radiopharmacy and chemistry 2023, Vol.8 (1)
• Main Authors: Wegrzyniak, Olivia, Zhang, Bo, Rokka, Johanna, Rosestedt, Maria, Mitran, Bogdan, Cheung, Pierre, Puuvuori, Emmi, Ingvast, Sofie, Persson, Jonas, Nordström, Helena, Löfblom, John, Pontén, Fredrik, Frejd, Fredrik Y., Korsgren, Olle, Eriksson, Jonas, Eriksson, Olof
• Format: Article
• Language: English
• Subjects: Fibrogenesis; Hepatic stellate cells; Liver fibrosis; PET imaging; Platelet derived growth factor receptor
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-023-00210-6

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: [Figure not available: see fulltext.]