title: Characterization of 5-(2-18F-fluoroethoxy)-L-tryptophan for PET imaging of the pancreas.
abstract: Purpose: In diabetes, pancreatic beta cell mass declines significantly prior to onset of fasting hyperglycemia. This decline may be due to endoplasmic reticulum (ER) stress, and the system L amino acid transporter LAT1 may be a biomarker of this process. In this study, we used 5-(2-18F-fluoroethoxy)-L-tryptophan (18F-L-FEHTP) to target LAT1 as a potential biomarker of beta cell function in diabetes.Procedures:Uptake of18F-L-FEHTP was determined in wild-type C57BL/6 mice byex vivobiodistribution. Both dynamic and static positron emission tomography (PET) images were acquired in wild-type and Akita mice, a model of ER stress-induced diabetes, as well as in mice treated with streptozotocin (STZ). LAT1 expression in both groups of mice was evaluated by immunofluorescence microscopy.Results:Uptake of18F-L-FEHTP was highest in the pancreas, and static PET images showed highly specific pancreatic signal. Time-activity curves showed significantly reduced18F-L-FEHTP uptake in Akita mice, and LAT1 expression was also reduced. However, mice treated with STZ, in which beta cell mass was reduced by 62%, showed no differences in18F-L-FEHTP uptake in the pancreas, and there was no significant correlation of18F-L-FEHTP uptake with beta cell mass.Conclusions:18F-L-FEHTP is highly specific for the pancreas with little background uptake in kidney or liver. We were able to detect changes in LAT1 in a mouse model of diabetes, but these changes did not correlate with beta cell function or mass. Therefore,18F-L-FEHTP PET is not a suitable method for the noninvasive imaging of changes in beta cell function during the progression of diabetes.
authors.affiliation: Department of Medical Biophysics, Western University, London, ON, N6A 5C1, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abbas
authors.affiliation: Metabolism and Diabetes Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Beamish
authors.affiliation: Metabolism and Diabetes Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada; Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: McGirr
authors.affiliation: Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Demarco
authors.affiliation: Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Cockburn
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors.forename: Dawid
authors.initials: D
authors.lastname: Krokowski
authors.affiliation: Department of Medical Biophysics, Western University, London, ON, N6A 5C1, Canada; Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada.
authors.forename: Ting-Yim
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Department of Medical Biophysics, Western University, London, ON, N6A 5C1, Canada; Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kovacs
authors.affiliation: Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Hatzoglou
authors.affiliation: Department of Medical Biophysics, Western University, London, ON, N6A 5C1, Canada; Metabolism and Diabetes Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada; Imaging Program, Lawson Health Research Institute, London, ON, N6A 4V2, Canada; Department of Pathology and Laboratory Medicine, Western University, London, ON, N6A 5C1, Canada.
authors.forename: Savita
authors.initials: S
authors.lastname: Dhanvantari
keywords: Akita mice; ER stress; LAT1; PET; beta cell; biomarker; diabetes; insulin; pancreas