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Non-invasive PET imaging of liver fibrogenesis using a RESCA-conjugated Affibody molecule
Uppsala Univ, Dept Med Chem, Sci Life Lab, Uppsala, Sweden..
Uppsala Univ, Dept Med Chem, Sci Life Lab, Uppsala, Sweden..
Uppsala Univ, Dept Med Chem, Sci Life Lab, Uppsala, Sweden.;Antaros Med AB, Mölndal, Sweden..
Uppsala Univ, Dept Med Chem, Sci Life Lab, Uppsala, Sweden..ORCID iD: 0000-0003-1330-9800
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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)
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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
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QC 20240905

Available from: 2024-09-05 Created: 2024-09-05 Last updated: 2024-09-05Bibliographically approved

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Persson, JonasLöfblom, John

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