Evaluation of [11C]-DAA1106 for imaging and quantification of neuroinflammation in a rat model of herpes encephalitis

Nuclear Medicine and Biology
Janine DoorduinE F J de Vries

Abstract

Many neurological and psychiatric disorders are associated with neuroinflammation. Positron emission tomography (PET) with [(11)C]-PK11195 can be used to study neuroinflammation in these disorders. However, [(11)C]-PK11195 may not be sensitive enough to visualize mild neuroinflammation. As a potentially more sensitive PET tracer for neuroinflammation, [(11)C]-N-(2,5-dimethoxybenzyl)-N-(4-fluoro-2-phenoxyphenyl)-acetamide (DAA1106) was evaluated in a rat model of herpes encephalitis. Male Wistar rats were intranasally inoculated with HSV-1 (HSE) or phosphate-buffered saline (control). At Day 6 or Day 7 after inoculation, small-animal [(11)C]-DAA1106 PET scans were acquired, followed by ex vivo biodistribution. Arterial blood sampling was performed for quantification of uptake. In HSE rats, a significantly higher ex vivo, but not in vivo, uptake of [(11)C]-DAA1106 was found in almost all examined brain areas (24-71%, P<.05), when compared to control rats. Pretreatment with unlabeled PK11195 effectively reduced [(11)C]-DAA1106 uptake in HSE rats (54-84%; P<.001). The plasma and brain time-activity curves showed rapid uptake of [(11)C]-DAA1106 into tissue. The data showed a good fit to the Logan analysis but could not be fitted to ...Continue Reading

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Citations

Oct 7, 2010·Pharmaceutical Research·Inge van RooyEnrico Mastrobattista
May 23, 2012·Glia·Sriram VennetiClayton A Wiley
Feb 12, 2014·NeuroImage·Soumen PaulAren van Waarde
Mar 17, 2015·European Journal of Nuclear Medicine and Molecular Imaging·David Vállez GarciaJanine Doorduin
Mar 19, 2014·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Mick M WellingLouise van der Weerd
Oct 11, 2012·International Journal of Molecular Imaging·Hans J C BuiterMarc C Huisman
May 3, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Andreas H JacobsUNKNOWN INMiND consortium
Feb 11, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Inês F AntunesErik F J de Vries

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