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

doi:10.1016/j.isci.2024.109688

Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule

iScience. 2024 Apr 10;27(5):109688. doi: 10.1016/j.isci.2024.109688. eCollection 2024 May 17.

Authors

Olivia Wegrzyniak¹, Francesco Lechi¹, Bogdan Mitran^{1

2}, Pierre Cheung¹, Athanasios Bitzios¹, Jonas Persson^{1

3}, John Löfblom³, Helena Nordström⁴, Jonas Eriksson^{1

5}, Fredrik Y Frejd^{6

7}, Olle Korsgren⁶, Bo Zhang¹, Olof Eriksson^{1

2}

Affiliations

¹ Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
² Antaros Medical AB, Mölndal, Sweden.
³ Department of Protein Science, Division of Protein Engineering, KTH Royal Institute of Technology, Stockholm, Sweden.
⁴ Science for Life Laboratory, Drug Discovery & Development Platform, Department of Chemistry-BMC, Uppsala University, Uppsala, Sweden.
⁵ PET Center, Uppsala University Hospital, Uppsala, Sweden.
⁶ Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
⁷ Affibody AB, Solna, Sweden.

Abstract

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.

Keywords: Biochemistry; Biological sciences; Biological sciences research methodologies; Biological sciences tools; Health sciences; Health technology; Natural sciences.