Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule
Olivia Wegrzyniak,
Francesco Lechi,
Bogdan Mitran,
Pierre Cheung,
Athanasios Bitzios,
Jonas Persson,
John Löfblom,
Helena Nordström,
Jonas Eriksson,
Fredrik Y. Frejd,
Olle Korsgren,
Bo Zhang,
Olof Eriksson
Affiliations
Olivia Wegrzyniak
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
Francesco Lechi
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
Bogdan Mitran
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden; Antaros Medical AB, Mölndal, Sweden
Pierre Cheung
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
Athanasios Bitzios
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
Jonas Persson
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden; Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
John Löfblom
Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden
Helena Nordström
Science for Life Laboratory, Drug Discovery & Development Platform, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden
Jonas Eriksson
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden; PET Center, Uppsala University Hospital, Uppsala, Sweden
Fredrik Y. Frejd
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Affibody AB, Solna, Sweden
Olle Korsgren
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
Bo Zhang
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
Olof Eriksson
Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden; Antaros Medical AB, Mölndal, Sweden; Corresponding author
Summary: Non-invasive assessment of fibrogenic activity, rather than fibrotic scars, could significantly improve the management of fibrotic diseases and the development of anti-fibrotic drugs. This study explores the potential of an Affibody molecule (Z09591) labeled with the Al(18)F-restrained complexing agent (RESCA) method as a tracer for the non-invasive detection of fibrogenic cells. Z09591 was functionalized with the RESCA chelator for direct labeling with [18F]AlF. In vivo positron emission tomography/magnetic resonance imaging scans on U-87 tumor-bearing mice exhibited high selectivity of the resulting radiotracer, [18F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor β (PDGFRβ), with minimal non-specific background uptake. Evaluation in a mouse model with carbon tetrachloride-induced fibrotic liver followed by a disease regression phase, revealed the radiotracer’s high affinity and specificity for fibrogenic cells in fibrotic livers (standardized uptake value [SUV] 0.43 ± 0.05), with uptake decreasing during recovery (SUV 0.29 ± 0.03) (p < 0.0001). [18F]AlF-RESCA-Z09591 accurately detects PDGFRβ, offering non-invasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development.
