1. PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[ 18 F]fluoro-6-deoxy-D-fructose.
- Author
-
Boyle, Amanda J., Murrell, Emily, Tong, Junchao, Schifani, Christin, Narvaez, Andrea, Wuest, Melinda, West, Frederick, Wuest, Frank, and Vasdev, Neil
- Subjects
POSITRON emission tomography ,METABOLIC models ,FRUCTOSE ,NEUROINFLAMMATION ,MICROGLIA ,POLYETHYLENE terephthalate ,TRANSLOCATOR proteins - Abstract
Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[
18 F]FDF) targets the fructose-preferred facilitative hexose transporter GLUT5, which is expressed predominantly in brain microglia and activated in response to inflammatory stimuli. We hypothesize that 6-[18 F]FDF will specifically image microglia following neuroinflammatory insult. 6-[18 F]FDF and, for comparison, [18 F]FDG were evaluated in unilateral intra-striatal lipopolysaccharide (LPS)-injected male and female rats (50 µg/animal) by longitudinal dynamic PET imaging in vivo. In LPS-injected rats, increased accumulation of 6-[18 F]FDF was observed at 48 h post-LPS injection, with plateaued uptake (60–120 min) that was significantly higher in the ipsilateral vs. contralateral striatum (0.985 ± 0.047 and 0.819 ± 0.033 SUV, respectively; p = 0.002, n = 4M/3F). The ipsilateral–contralateral difference in striatal 6-[18 F]FDF uptake expressed as binding potential (BPSRTM ) peaked at 48 h (0.19 ± 0.11) and was significantly decreased at one and two weeks. In contrast, increased [18 F]FDG uptake in the ipsilateral striatum was highest at one week post-LPS injection (BPSRTM = 0.25 ± 0.06, n = 4M). Iba-1 and GFAP immunohistochemistry confirmed LPS-induced activation of microglia and astrocytes, respectively, in ipsilateral striatum. This proof-of-concept study revealed an early response of 6-[18 F]FDF to neuroinflammatory stimuli in rat brain. 6-[18 F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in brain with applications in neuroinflammatory and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF