title: Systematic screening of imaging biomarkers for the Islets of Langerhans, among clinically available positron emission tomography tracers.
abstract: BACKGROUND
  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 [(11)C]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, [(11)C]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.
authors.affiliation: Preclinical PET Platform, department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
authors.forename: Filip
authors.initials: F
authors.lastname: Karlsson
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Pantelis Clewemar
authors.initials: PC
authors.lastname: Antonodimitrakis
authors.affiliation: Preclinical PET Platform, department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden. Electronic address: olof.eriksson@pet.medchem.uu.se.
authors.forename: Olof
authors.initials: O
authors.lastname: Eriksson
mesh_terms: D000465:Algorithms; D001692:Biological Transport; D015415:Biomarkers / Q000378:metabolism; D003198:Computer Simulation; D006801:Humans; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011849:Radioactive Tracers
chemical_list: D015415:Biomarkers; D011849:Radioactive Tracers
keywords: Beta cell imaging; Endocrine; Islet imaging; Islets of Langerhans; Pancreas; Positron emission tomography