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Systematic screening of imaging biomarkers for the Islets of Langerhans, among clinically available positron emission tomography tracers
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Preclinical PET Platform.
2015 (English)In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 42, no 10, 762-769 p.Article in journal (Refereed) Published
Abstract [en]

Introduction: Functional imaging could be utilized for visualizing pancreatic islets of Langerhans. Therefore, we present a stepwise algorithm for screening of clinically available positron emission tomography (PET) tracers for their use in imaging of the neuroendocrine pancreas in the context of diabetes. Methods: A stepwise procedure was developed for screening potential islet imaging agents. Suitable PET-tracer candidates were identified by their molecular mechanism of targeting. Clinical abdominal examinations were retrospectively analyzed for pancreatic uptake and retention. The target protein localization in the pancreas was assessed in silico by -omics approaches and the in vitro by binding assays to human pancreatic tissue. Results: Six putative candidates were identified and screened by using the stepwise procedure. Among the tested PET tracers, only [C-11]5-Hydroxy-tryptophan passed all steps. The remaining identified candidates were falsified as candidates and discarded following in silico and in vitro screening. Conclusions: Of the six clinically available PET tracers identified, [C-11]5-HTP was found to be a promising candidate for beta cell imaging, based on intensity of in vivo pancreatic uptake in humans, and islet specificity as assessed on human pancreatic cell preparations. The flow scheme described herein constitutes a methodology for evaluating putative islet imaging biomarkers among clinically available PET tracers.

Place, publisher, year, edition, pages
2015. Vol. 42, no 10, 762-769 p.
Keyword [en]
Beta cell imaging, Islet imaging, Positron emission tomography, Pancreas, Islets of Langerhans, Endocrine
National Category
Endocrinology and Diabetes Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-264613DOI: 10.1016/j.nucmedbio.2015.06.004ISI: 000361423700002PubMedID: 26138288OAI: oai:DiVA.org:uu-264613DiVA: diva2:865299
Funder
Swedish Child Diabetes FoundationSwedish Diabetes Association
Available from: 2015-10-27 Created: 2015-10-15 Last updated: 2017-12-01Bibliographically approved

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Antonodimitrakis, Pantelis ClewemarEriksson, Olof

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