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.

Cyclooxygenase-2 (COX-2) is a target for inflammation and colorectal cancer (CRC). This study evaluated the COX-2 neuro-PET radiopharmaceutical, [ 11 C]MC1, in CRC xenograft mice. Procedures: [ 11 C]MC1 was evaluated in ICRscid mice with HT-29 and HCT-116 CRC xenografts, with high and low COX-2 expression, respectively, by immunohistochemistry, cellular uptake, dynamic PET/MR imaging, ex vivo biodistribution, and radiometabolite analysis. Results: HT-29 xenografts were well visualized with [ 11 C]MC1 using PET/MR. Time-activity curves revealed steady tumor radioactivity accumulation in HT-29 xenografts that plateaued from 40 to 60 min (3.07 ± 0.65 %ID/g) and was significantly reduced by pre-treatment with MC1 or celecoxib (1.62 ± 0.29 and 1.18 ± 0.21 %ID/g, respectively, p = 0.045 and p = 0.005). Radiometabolite analysis showed that [ 11 C]MC1 accounted for >90 % of tumor radioactivity, with <10 % in plasma, at 40 min post-injection of the radiotracer. Conclusions: [ 11 C]MC1 is a promising PET imaging agent for COX-2 in CRC and translation for cancer research should be considered.

Introduction: Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[18F]FDF) was developed for PET imaging of fructose metabolism in breast cancer via the fructose-preferred facilitative hexose transporter, GLUT5. In the brain, GLUT5 is predominantly expressed on microglial cells that are activated in response to inflammatory stimuli. We hypothesize that 6-[18F]FDF will specifically image microglia following neuroinflammatory insult. Methods: 6-[18F]FDF was evaluated in a neuroinflammation model induced by unilateral injection of lipopolysaccharide (LPS) into the right striatum (50 µg/animal) in male and female rats. Comparison of 6-[18F]FDF and the glucose derivative [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG), was performed by longitudinal dynamic PET imaging in vivo. Immunohistochemistry was conducted to examine the presence of activated microglia (Iba-1) and astrocytes (GFAP) in fixed brain tissues. Results: In LPS-injected rats, increased accumulation of radioactivity from 6-[18F]FDF was observed in the ipsilateral striatum compared to the contralateral side at 24-48 hr post-LPS injection, with plateaued uptake at 60-120 min significantly higher in the right (0.985 ± 0.047 SUV) vs. left (0.819 ± 0.033 SUV) striatum at 48 h (P = 0.002; n = 4M/3F). The ipsilateral-contralateral difference in striatal 6-[18F]FDF uptake expressed as binding potential peaked at 48 h (male: 0.25 ± 0.03; female: 0.11 ± 0.03) and was significantly decreased at later time points of one, two and four weeks; and was higher in male rats (P = 0.017). In contrast, increased [18F]FDG uptake was observed in the ipsilateral striatum compared to the contralateral striatum and was highest at one week post-LPS injection. Iba-1 and GFAP immunohistochemistry confirmed LPS-induced activation of microglia and astrocytes in the ipsilateral striatum. Conclusions: 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 the brain with applications in neuroinflammatory and neurodegenerative diseases.