PT  - JOURNAL ARTICLE
AU  - Inês F. Antunes
AU  - Janine Doorduin
AU  - Hidde J. Haisma
AU  - Philip H. Elsinga
AU  - Aren van Waarde
AU  - Antoon T.M. Willemsen
AU  - Rudi A. Dierckx
AU  - Erik F.J. de Vries
TI  - <sup>18</sup>F-FEAnGA for PET of β-Glucuronidase Activity in Neuroinflammation
AID  - 10.2967/jnumed.111.096388
DP  - 2012 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 451--458
VI  - 53
IP  - 3
4099  - http://jnm.snmjournals.org/content/53/3/451.short
4100  - http://jnm.snmjournals.org/content/53/3/451.full
SO  - J Nucl Med2012 Mar 01; 53
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.