| 18F-FEAnGA for PET of β-Glucuronidase Activity in Neuroinflammation. | |
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MedLine Citation:
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PMID: 22323774 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Inês F Antunes; Janine Doorduin; Hidde J Haisma; Philip H Elsinga; Aren van Waarde; Antoon T M Willemsen; Rudi A Dierckx; Erik F J de Vries |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-8 |
Journal Detail:
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Title: Journal of nuclear medicine : official publication, Society of Nuclear Medicine Volume: - ISSN: 1535-5667 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217410 Medline TA: J Nucl Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands; and. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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