Filip Karlsson1, Pantelis Clewemar Antonodimitrakis2, Olof Eriksson3. 1. Preclinical PET Platform, department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden. 2. Department of Medical Sciences, Uppsala University, Uppsala, Sweden. 3. Preclinical PET Platform, department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden. Electronic address: olof.eriksson@pet.medchem.uu.se.
Abstract
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 [(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.
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 humanpancreatic 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 humanpancreatic cell preparations. The flow scheme described herein constitutes a methodology for evaluating putative islet imaging biomarkers among clinically available PET tracers.
Authors: Jason Bini; Mika Naganawa; Nabeel Nabulsi; Yiyun Huang; Jim Ropchan; Keunpoong Lim; Soheila Najafzadeh; Kevan C Herold; Gary W Cline; Richard E Carson Journal: J Nucl Med Date: 2018-01-25 Impact factor: 10.057