Journal Article

Towards PET Imaging of Intact Pancreatic Beta Cell Mass: A Transgenic Strategy

Kovacs, Michael S., Dhanvantari, Savita, Hu, Shirley, Lee, Ting-Yim, McGirr, Rebecca, Yee, Siu-Pok

2011

Overview

Purpose We have generated transgenic mouse lines expressing the positron emission tomography (PET) reporter gene, sr39tk , under the control of the mouse insulin I promoter (MIP-sr39tk) to image endogenous islets using PET. Procedures The MIP-sr39tk transgene was constructed using the 8.3 kb fragment of the mouse insulin I promoter and the sr39tk coding sequence from the mrfp-hrl-ttk trifusion construct. Expression of sr39TK in beta cells was confirmed by fluorescence immunohistochemistry of pancreatic sections. Histological sections were used to determine beta cell mass, islet area and islet number. Beta cell function was determined using intraperitoneal glucose tolerance tests. For ex vivo biodistrubution, mice were injected i.v. with 9.25 MBq [ 18 F]fluorohydroxymethyl-butyl-guanine (FHBG), euthanized 1 h later and pancreata and other organs were collected and counted. For PET scans, mice were injected i.v. with 9.25 MBq [ 18 F]FHBG, and dynamic scans were conducted for 1 h, followed by a 30 min static acquisition. To induce type 1 diabetes-like symptoms, MIP-sr39tk mice were injected i.p. with 40 mg/kg streptozotocin (STZ) once per day for five consecutive days, and biodistribution and PET scans were conducted thereafter. Results Ex vivo quantification of [ 18 F]FHBG uptake in the pancreas showed a 4.5-fold difference in transgenic vs . non-transgenics, confirming that expression of sr39TK results in the retention of the PET tracer. In STZ-treated MIP-sr39tk mice, impairments in glucose tolerance and decreases in beta cell mass correlated significantly with a diminishment in [ 18 F]FHBG uptake before fasting hyperglycemia became apparent. Conclusions The MIP-sr39tk mouse demonstrates that PET imaging can detect changes in beta cell mass that precede the onset of diabetes.

• Publisher: Springer-Verlag,Springer Nature B.V
• Subject: Animals / Base Sequence / Blotting, Western / DNA Primers / Glucose Tolerance Test / Imaging / Immunohistochemistry / Islets of Langerhans - diagnostic imaging / Medicine / Medicine & Public Health / Mice / Mice, Transgenic / Polymerase Chain Reaction / Positron-Emission Tomography / Radiology / Research Article / Tissue Distribution