RT Journal Article SR Electronic T1 18F-FEAnGA for PET of β-Glucuronidase Activity in Neuroinflammation JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 451 OP 458 DO 10.2967/jnumed.111.096388 VO 53 IS 3 A1 Inês F. Antunes A1 Janine Doorduin A1 Hidde J. Haisma A1 Philip H. Elsinga A1 Aren van Waarde A1 Antoon T.M. Willemsen A1 Rudi A. Dierckx A1 Erik F.J. de Vries YR 2012 UL http://jnm.snmjournals.org/content/53/3/451.abstract AB 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.