%0 Journal Article %A Inês F. Antunes %A Janine Doorduin %A Hidde J. Haisma %A Philip H. Elsinga %A Aren van Waarde %A Antoon T.M. Willemsen %A Rudi A. Dierckx %A Erik F.J. de Vries %T 18F-FEAnGA for PET of β-Glucuronidase Activity in Neuroinflammation %D 2012 %R 10.2967/jnumed.111.096388 %J Journal of Nuclear Medicine %P 451-458 %V 53 %N 3 %X 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 18F-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. 11C-(R)-PK11195 and 18F-FEAnGA small-animal PET scans were acquired for 60 min. Logan graphical analysis was used to calculate 18F-FEAnGA distribution volumes (DVLogan) in various brain areas. Results: After administration of 18F-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 DVLogan of 18F-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 18F-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 DVLogan of 18F-FEAnGA in the same areas of the brain. Furthermore, the DVLogan of 18F-FEAnGA also correlated with β-glucuronidase activity in the same brain regions. In addition, DVLogan of 18F-FEAnGA showed a tendency to correlate with 11C-(R)-PK11195 uptake (marker for activated microglia) in the same brain regions. Conclusion: Despite relatively low brain uptake, 18F-FEAnGA was able to detect an increased release of β-glucuronidase during neuroinflammation. %U https://jnm.snmjournals.org/content/jnumed/53/3/451.full.pdf