Abstract

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.

Details

Title
Imaging of fibrogenesis in the liver by [18F]TZ-Z09591, an Affibody molecule targeting platelet derived growth factor receptor β
Author
Wegrzyniak, Olivia 1   VIAFID ORCID Logo  ; Zhang, Bo 1 ; Rokka, Johanna 2 ; Rosestedt, Maria 1 ; Mitran, Bogdan 3 ; Cheung, Pierre 1 ; Puuvuori, Emmi 1 ; Ingvast, Sofie 2 ; Persson, Jonas 4 ; Nordström, Helena 5 ; Löfblom, John 6 ; Pontén, Fredrik 2 ; Frejd, Fredrik Y. 7 ; Korsgren, Olle 2 ; Eriksson, Jonas 8 ; Eriksson, Olof 3 

1  Uppsala University, Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
2  Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
3  Uppsala University, Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457); Antaros Medical AB, Uppsala, Sweden (GRID:grid.511796.d) 
4  Uppsala University, Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457); KTH Royal Institute of Technology, Department of Protein Science, Division of Protein Engineering, Stockholm, Sweden (GRID:grid.5037.1) (ISNI:0000 0001 2158 1746) 
5  Uppsala University, Science for Life Laboratory, Drug Discovery and Development Platform, Department of Chemistry-BMC, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457) 
6  KTH Royal Institute of Technology, Department of Protein Science, Division of Protein Engineering, Stockholm, Sweden (GRID:grid.5037.1) (ISNI:0000 0001 2158 1746) 
7  Uppsala University, Department of Immunology, Genetics and Pathology, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457); Affibody AB, Solna, Sweden (GRID:grid.451532.4) (ISNI:0000 0004 0467 9487) 
8  Uppsala University, Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala, Sweden (GRID:grid.8993.b) (ISNI:0000 0004 1936 9457); Uppsala University Hospital PET Center, Uppsala, Sweden (GRID:grid.412354.5) (ISNI:0000 0001 2351 3333) 
Pages
23
Publication year
2023
Publication date
Dec 2023
Publisher
Springer Nature B.V.
e-ISSN
2365-421X
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1186/s41181-023-00210-6
ProQuest document ID
2866957957
Copyright
© The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.