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Pancreatic imaging using an antibody fragment targeting the zinc transporter type 8: a direct comparison with radio-iodinated Exendin-4
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.ORCID iD: 0000-0002-8524-9547
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry.
Mellitech SAS, Grenoble, France.
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2018 (English)In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 55, no 1, p. 49-57Article in journal (Refereed) Published
Abstract [en]

AIM: The zinc transporter 8 (ZnT8) has been suggested as a suitable target for non-invasive visualization of the functional pancreatic beta cell mass, due to both its pancreatic beta cell restricted expression and tight involvement in insulin secretion.

METHODS: In order to examine the potential of ZnT8 as a surrogate target for beta cell mass, we performed mRNA transcription analysis in pancreatic compartments. A novel ZnT8 targeting antibody fragment Ab31 was radiolabeled with iodine-125, and evaluated by in vitro autoradiography in insulinoma and pancreas as well as by in vivo biodistribution. The evaluation was performed in a direct comparison with radio-iodinated Exendin-4.

RESULTS: Transcription of the ZnT8 mRNA was higher in islets of Langerhans compared to exocrine tissue. Ab31 targeted ZnT8 in the cytosol and on the plasma membrane with 108 nM affinity. Ab31 was successfully radiolabeled with iodine-125 with high yield and > 95% purity. [(125)I]Ab31 binding to insulinoma and pancreas was higher than for [(125)I]Exendin-4, but could only by partially competed away by 200 nM Ab31 in excess. The in vivo uptake of [(125)I]Ab31 was higher than [(125)I]Exendin-4 in most tissues, mainly due to slower clearance from blood.

CONCLUSIONS: We report a first-in-class ZnT8 imaging ligand for pancreatic imaging. Development with respect to ligand miniaturization and radionuclide selection is required for further progress. Transcription analysis indicates ZnT8 as a suitable target for visualization of the human endocrine pancreas.

Place, publisher, year, edition, pages
Springer, 2018. Vol. 55, no 1, p. 49-57
Keywords [en]
Ab31, Beta cell imaging, Imaging, Islet imaging, Type 2 diabetes, Zinc Transport type 8
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-334594DOI: 10.1007/s00592-017-1059-xISI: 000424018600006PubMedID: 29064047OAI: oai:DiVA.org:uu-334594DiVA, id: diva2:1160029
Funder
Swedish Child Diabetes FoundationErnfors FoundationAvailable from: 2017-11-24 Created: 2017-11-24 Last updated: 2019-06-27Bibliographically approved

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Eriksson, OlofKorsgren, OlleSelvaraju, Ram KumarAltai, Mohamed

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