Imaging Pancreas in Healthy and Diabetic Rodent Model Using [ 18 F]Fallypride Positron Emission Tomography/Computed Tomography

Abstract

Background:

A noninvasive method of monitoring the loss of islet cells can provide an earlier and improved diagnosis for therapeutics development of preclinical phases of diabetes. The use of [¹⁸F]fallypride, a dopamine D2/D3 receptor radiotracer, has been developed as a surrogate marker to evaluate loss of pancreatic islet cells in a rodent model of type 1 diabetes.

Materials and Methods:

Healthy Sprague–Dawley rats were administered [¹⁸F]fallypride and imaged for 2 h in a positron emission tomography (PET)/computed tomography (CT) scan. Diabetes was then induced in the same rats by administration of streptozotocin, and a PET/CT scan was performed 4 days after establishing diabetes. Pancreata of a separate set of rats were evaluated by insulin immunostaining for loss of islet cells by streptozotocin.

Results:

Blood glucose levels of 125 mg/dL and 550 mg/dL were established for those rats without and with diabetes, respectively. [¹⁸F]Fallypride uptake in the pancreas of both groups of rats was rapid, but the rats with diabetes showed a significantly lower uptake (less than 50%). The specific binding ratio was decreased by 77% in the diabetic rats.

Conclusions:

[¹⁸F]Fallypride can be a useful surrogate marker for monitoring changes in pancreatic islet cells, thus providing a noninvasive method to evaluate efficacy of therapeutics.