Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β.
- Resource Type
- Article
- 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
- Source
- EJNMMI Radiopharmacy & Chemistry. 9/21/2023, Vol. 8 Issue 1, p1-18. 18p.
- Subject
- *PLATELET-derived growth factor
*PLATELET-derived growth factor receptors
*LIVER cells
*POSITRON emission tomography
*LIVER
*OPIOID receptors
- Language
- ISSN
- 2365-421X
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. [ABSTRACT FROM AUTHOR]