Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody moleculeShow others and affiliations
2024 (English)In: iScience, E-ISSN 2589-0042, Vol. 27, no 5, article id 109688Article in journal (Refereed) Published
Abstract [en]
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. 18 F]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, 18 F]AlF-RESCA-Z09591, for platelet-derived growth factor receptor b (PDGFRb), b ), 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 p < 0.0001). [18F]AlF-RESCA-Z09591 18 F]AlF-RESCA-Z09591 accurately detects PDGFRb, b, offering noninvasive assessment of fibrogenic cells and promising applications in precise liver fibrogenesis diagnosis, potentially contributing significantly to anti-fibrotic drug development.
Place, publisher, year, edition, pages
Elsevier BV , 2024. Vol. 27, no 5, article id 109688
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:kth:diva-352690DOI: 10.1016/j.isci.2024.109688ISI: 001288013000001PubMedID: 38660405Scopus ID: 2-s2.0-85190730166OAI: oai:DiVA.org:kth-352690DiVA, id: diva2:1895292
Note
QC 20240905
2024-09-052024-09-052024-09-05Bibliographically approved