PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[18F]fluoro-6-deoxy-D-fructose

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 23; p. 8529
• Main Authors: Boyle, Amanda J., Murrell, Emily, Tong, Junchao, Schifani, Christin, Narvaez, Andrea, Wuest, Melinda, West, Frederick, Wuest, Frank, Vasdev, Neil
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.12.2022; MDPI
• Subjects: Alzheimer's disease; Animals; Biomarkers; Brain; Brain - diagnostic imaging; Brain - metabolism; Breast cancer; Communication; Female; Females; fluorine-18; Fluorodeoxyglucose F18; fructose; Fructose - metabolism; Glucose; GLUT5; Ligands; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Male; Metabolism; microglia; neuroinflammation; PET; Positron-Emission Tomography - methods; Rats; Rodentia - metabolism; Rodents; fluorine-18; neuroinflammation; FDG; FDF; fructose; GLUT5; microglia; PET
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27238529

Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[18F]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-[18F]FDF will specifically image microglia following neuroinflammatory insult. 6-[18F]FDF and, for comparison, [18F]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-[18F]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-[18F]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 [18F]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-[18F]FDF to neuroinflammatory stimuli in rat brain. 6-[18F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in brain with applications in neuroinflammatory and neurodegenerative diseases.