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

Olivia Wegrzyniak; Bo Zhang; Johanna Rokka; Maria Rosestedt; Bogdan Mitran; Pierre Cheung; Emmi Puuvuori; Sofie Ingvast; Jonas Persson; Helena Nordström; John Löfblom; Fredrik Pontén; Fredrik Y Frejd; Olle Korsgren; Jonas Eriksson; Olof Eriksson

doi:10.1186/s41181-023-00210-6

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

EJNMMI Radiopharm Chem. 2023 Sep 21;8(1):23. doi: 10.1186/s41181-023-00210-6.

Authors

Olivia Wegrzyniak¹, Bo Zhang¹, Johanna Rokka², Maria Rosestedt¹, Bogdan Mitran^{1

3}, Pierre Cheung¹, Emmi Puuvuori¹, Sofie Ingvast², Jonas Persson^{1

4}, Helena Nordström⁵, John Löfblom⁴, Fredrik Pontén², Fredrik Y Frejd^{2

6}, Olle Korsgren², Jonas Eriksson^{7

8}, Olof Eriksson^{9

10}

Affiliations

¹ Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden.
² Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
³ Antaros Medical AB, Uppsala, Sweden.
⁴ Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden.
⁵ Science for Life Laboratory, Drug Discovery and Development Platform, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
⁶ Affibody AB, Solna, Sweden.
⁷ Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden. jonas.p.eriksson@akademiska.se.
⁸ Uppsala University Hospital PET Center, Entrance 85, Dag Hammarskjölds Väg 21, 752 37, Uppsala, Sweden. jonas.p.eriksson@akademiska.se.
⁹ Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden. olof.eriksson@ilk.uu.se.
¹⁰ Antaros Medical AB, Uppsala, Sweden. olof.eriksson@ilk.uu.se.

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.

Keywords: Fibrogenesis; Hepatic stellate cells; Liver fibrosis; PET imaging; Platelet derived growth factor receptor.