Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β.

Wegrzyniak O, Zhang B, Rokka J, Rosestedt M, Mitran B, Cheung P, Puuvuori E, Ingvast S, Persson J, Nordström H, Löfblom J, Pontén F, Frejd FY, Korsgren O, Eriksson J, Eriksson O

EJNMMI Radiopharm Chem 8 (1) 23 [2023-09-21; online 2023-09-21]

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. 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. 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.

Drug Discovery and Development (DDD) [Collaborative]

PubMed 37733133

DOI 10.1186/s41181-023-00210-6

Crossref 10.1186/s41181-023-00210-6

pmc: PMC10513984
pii: 10.1186/s41181-023-00210-6