PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose
Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[<sup>18</sup>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-[<sup>18</su...
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/23/8529 |
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| author | Amanda J. Boyle Emily Murrell Junchao Tong Christin Schifani Andrea Narvaez Melinda Wuest Frederick West Frank Wuest Neil Vasdev |
| author_facet | Amanda J. Boyle Emily Murrell Junchao Tong Christin Schifani Andrea Narvaez Melinda Wuest Frederick West Frank Wuest Neil Vasdev |
| author_sort | Amanda J. Boyle |
| collection | DOAJ |
| description | Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[<sup>18</sup>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-[<sup>18</sup>F]FDF will specifically image microglia following neuroinflammatory insult. 6-[<sup>18</sup>F]FDF and, for comparison, [<sup>18</sup>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-[<sup>18</sup>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; <i>p</i> = 0.002, n = 4M/3F). The ipsilateral–contralateral difference in striatal 6-[<sup>18</sup>F]FDF uptake expressed as binding potential (<i>BP</i><sub>SRTM</sub>) peaked at 48 h (0.19 ± 0.11) and was significantly decreased at one and two weeks. In contrast, increased [<sup>18</sup>F]FDG uptake in the ipsilateral striatum was highest at one week post-LPS injection (<i>BP</i><sub>SRTM</sub> = 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-[<sup>18</sup>F]FDF to neuroinflammatory stimuli in rat brain. 6-[<sup>18</sup>F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in brain with applications in neuroinflammatory and neurodegenerative diseases. |
| first_indexed | 2024-03-09T17:39:06Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T17:39:06Z |
| publishDate | 2022-12-01 |
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| series | Molecules |
| spelling | doaj.art-d531225683494a0aba71ae30763737172023-11-24T11:43:50ZengMDPI AGMolecules1420-30492022-12-012723852910.3390/molecules27238529PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructoseAmanda J. Boyle0Emily Murrell1Junchao Tong2Christin Schifani3Andrea Narvaez4Melinda Wuest5Frederick West6Frank Wuest7Neil Vasdev8Azrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaAzrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaAzrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaAzrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaAzrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaDepartment of Chemistry, University of Alberta, Edmonton, AB T6G 2N4, CanadaDepartment of Chemistry, University of Alberta, Edmonton, AB T6G 2N4, CanadaDepartment of Chemistry, University of Alberta, Edmonton, AB T6G 2N4, CanadaAzrieli Centre for Neuro-Radiochemistry, Brain Health Imaging Centre, Centre for Addiction and Mental Health, 250 College St., Toronto, ON M5T 1R8, CanadaFluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[<sup>18</sup>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-[<sup>18</sup>F]FDF will specifically image microglia following neuroinflammatory insult. 6-[<sup>18</sup>F]FDF and, for comparison, [<sup>18</sup>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-[<sup>18</sup>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; <i>p</i> = 0.002, n = 4M/3F). The ipsilateral–contralateral difference in striatal 6-[<sup>18</sup>F]FDF uptake expressed as binding potential (<i>BP</i><sub>SRTM</sub>) peaked at 48 h (0.19 ± 0.11) and was significantly decreased at one and two weeks. In contrast, increased [<sup>18</sup>F]FDG uptake in the ipsilateral striatum was highest at one week post-LPS injection (<i>BP</i><sub>SRTM</sub> = 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-[<sup>18</sup>F]FDF to neuroinflammatory stimuli in rat brain. 6-[<sup>18</sup>F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in brain with applications in neuroinflammatory and neurodegenerative diseases.https://www.mdpi.com/1420-3049/27/23/8529fructoseneuroinflammationPETfluorine-18GLUT5microglia |
| spellingShingle | Amanda J. Boyle Emily Murrell Junchao Tong Christin Schifani Andrea Narvaez Melinda Wuest Frederick West Frank Wuest Neil Vasdev PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose Molecules fructose neuroinflammation PET fluorine-18 GLUT5 microglia |
| title | PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose |
| title_full | PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose |
| title_fullStr | PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose |
| title_full_unstemmed | PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose |
| title_short | PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[<sup>18</sup>F]fluoro-6-deoxy-D-fructose |
| title_sort | pet imaging of fructose metabolism in a rodent model of neuroinflammation with 6 sup 18 sup f fluoro 6 deoxy d fructose |
| topic | fructose neuroinflammation PET fluorine-18 GLUT5 microglia |
| url | https://www.mdpi.com/1420-3049/27/23/8529 |
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