Imaging of fibrogenesis in the liver by [18F]TZ-Z0959: an Affibody molecule targeting platelet derived growth factor receptor βScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden; Antaros Medical AB, Uppsala, Sweden.
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden.
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering. KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden.
Science for Life Laboratory, Drug Discovery and Development Platform, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Affibody AB, Solna, Sweden.
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden; Uppsala University Hospital PET Center, Entrance 85, Dag Hammarskjölds Väg 21, 752 37, Uppsala, Sweden.
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds Väg 14C, 3tr, 751 83, Uppsala, Sweden; Antaros Medical AB, Uppsala, Sweden.
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2023 (English)In: EJNMMI Radiopharmacy and Chemistry, E-ISSN 2365-421X, Vol. 8, no 1, article id 23Article in journal (Refereed) Published
Abstract [en]
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.]
Place, publisher, year, edition, pages
Springer Nature , 2023. Vol. 8, no 1, article id 23
Keywords [en]
Fibrogenesis, Hepatic stellate cells, Liver fibrosis, PET imaging, Platelet derived growth factor receptor
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:kth:diva-337422DOI: 10.1186/s41181-023-00210-6ISI: 001075551000001PubMedID: 37733133Scopus ID: 2-s2.0-85171889532OAI: oai:DiVA.org:kth-337422DiVA, id: diva2:1802063
Note
QC 20231003
2023-10-032023-10-032023-10-30Bibliographically approved