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18F-FEAnGA for PET of β-glucuronidase activity in neuroinflammation
Inês F Antunes1, Janine Doorduin, Hidde J Haisma
1Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands.
Unlabelled:
Activation of microglia is a hallmark of inflammatory, infectious, and degenerative diseases of the central nervous system. Several studies have indicated that there is an increase in release of β-glucuronidase by activated microglia into the extracellular space at the site of neuroinflammation. β-glucuronidase is involved in the hydrolysis of glycosaminoglycans on the cell surface and the degradation of the extracellular matrix. Therefore, β-glucuronidase might be a biomarker for ongoing neurodegeneration induced by neuroinflammation. In this study, we investigated whether the PET tracer (18)F-FEAnGA was able to detect β-glucuronidase release during neuroinflammation in a rat model of herpes encephalitis.
Methods:
Male Wistar rats were intranasally inoculated with herpes simplex virus 1 (HSV-1) or phosphate-buffered saline as a control. (11)C-(R)-PK11195 and (18)F-FEAnGA small-animal PET scans were acquired for 60 min. Logan graphical analysis was used to calculate (18)F-FEAnGA distribution volumes (DV(Logan)) in various brain areas.
Results:
After administration of (18)F-FEAnGA, the area under the activity concentration-versus-time curve of the whole brain was 2 times higher in HSV-1-infected rats than in control rats. In addition, the DV(Logan) of (18)F-FEAnGA was most increased in the frontopolar cortex, frontal cortex, bulbus olfactorius, cerebral cortex, cerebellum, and brainstem of HSV-1-infected rats, when compared with control rats. The conversion of (18)F-FEAnGA to 4-hydroxy-3-nitrobenzyl alcohol was found to be 1.6 times higher in HSV-1-infected rats than in control rats and correlated with the DV(Logan) of (18)F-FEAnGA in the same areas of the brain. Furthermore, the DV(Logan) of (18)F-FEAnGA also correlated with β-glucuronidase activity in the same brain regions. In addition, DV(Logan) of (18)F-FEAnGA showed a tendency to correlate with (11)C-(R)-PK11195 uptake (marker for activated microglia) in the same brain regions.
Conclusion:
Despite relatively low brain uptake, (18)F-FEAnGA was able to detect an increased release of β-glucuronidase during neuroinflammation.
Insights
This study shows that the PET tracer (18)F-FEAnGA can detect increased beta-glucuronidase release in the brain during neuroinflammation, suggesting its potential as a biomarker for neurodegeneration. This finding aids in understanding and diagnosing central nervous system diseases.
Area of Science:
- Neuroscience
- Radiochemistry
- Biomarker Discovery
Background:
- Microglial activation is a key indicator in central nervous system diseases.
- Increased beta-glucuronidase release by activated microglia suggests it as a potential neurodegeneration biomarker.
- The PET tracer (18)F-FEAnGA was explored for detecting beta-glucuronidase in neuroinflammation.
Purpose of the Study:
- To investigate the utility of the PET tracer (18)F-FEAnGA in detecting beta-glucuronidase release during neuroinflammation.
- To evaluate (18)F-FEAnGA as a potential biomarker for neurodegeneration in a rat model of herpes encephalitis.
Main Methods:
- Male Wistar rats were infected with herpes simplex virus 1 (HSV-1) or a control.
- Small-animal PET scans were performed using (11)C-(R)-PK11195 and (18)F-FEAnGA.
- Logan graphical analysis determined (18)F-FEAnGA distribution volumes (DV(Logan)) in brain regions.
Main Results:
- HSV-1 infected rats showed a 2-fold higher area under the curve for (18)F-FEAnGA in the whole brain compared to controls.
- (18)F-FEAnGA DV(Logan) was significantly increased in multiple brain areas of infected rats.
- Increased (18)F-FEAnGA conversion and DV(Logan) correlated with beta-glucuronidase activity and showed a tendency to correlate with microglial activation markers.
Conclusions:
- The PET tracer (18)F-FEAnGA successfully detected increased beta-glucuronidase release in a rat model of neuroinflammation.
- Despite limited brain uptake, (18)F-FEAnGA shows promise for imaging neuroinflammation and neurodegeneration.
- (18)F-FEAnGA may serve as a valuable tool for diagnosing and monitoring central nervous system inflammatory conditions.
