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In Vivo Visualization of beta-Cells by Targeting of GPR44
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för läkemedelskemi, Theranostics.
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Karolinska Institutet and Stockholm County Council, Stockholm, Sweden.
Vise andre og tillknytning
2018 (engelsk)Inngår i: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 67, nr 2, s. 182-192Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

GPR44 expression has recently been described as highly beta-cell selective in the human pancreas and constitutes a tentative surrogate imaging biomarker in diabetes. A radiolabeled small-molecule GPR44 antagonist, [C-11]AZ12204657, was evaluated for visualization of beta-cells in pigs and non-human primates by positron emission tomography as well as in immunodeficient mice transplanted with human islets under the kidney capsule. In vitro autoradiography of human and animal pancreatic sections from subjects without and with diabetes, in combination with insulin staining, was performed to assess beta-cell selectivity of the radiotracer. Proof of principle of in vivo targeting of human islets by [C-11]AZ12204657 was shown in the immunodeficient mouse transplantation model. Furthermore, [C-11]AZ12204657 bound by a GPR44-mediated mechanism in pancreatic sections from humans and pigs without diabetes, but not those with diabetes. In vivo [C-11]AZ12204657 bound specifically to GPR44 in pancreas and spleen and could be competed away dose-dependently in nondiabetic pigs and nonhuman primates. [C-11]AZ12204657 is a first-in-class surrogate imaging biomarker for pancreatic beta-cells by targeting the protein GPR44.

sted, utgiver, år, opplag, sider
2018. Vol. 67, nr 2, s. 182-192
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Identifikatorer
URN: urn:nbn:se:uu:diva-342900DOI: 10.2337/db17-0764ISI: 000426034500003PubMedID: 29208633OAI: oai:DiVA.org:uu-342900DiVA, id: diva2:1185330
Forskningsfinansiär
Swedish Research Council, K2015-54X-12219-19-4, K2013-64X-08268-26-3, K2013-55X-15043, 921-2014-7054Ernfors FoundationGöran Gustafsson Foundation for Research in Natural Sciences and MedicineSwedish Child Diabetes FoundationSwedish Diabetes AssociationEXODIAB - Excellence of Diabetes Research in SwedenTilgjengelig fra: 2018-02-23 Laget: 2018-02-23 Sist oppdatert: 2018-05-09bibliografisk kontrollert

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