TY - JOUR T1 - <strong>Brain aromatase imaging in an acute neuroinflammation model </strong> <strong>using µPET and <sup>11</sup>C-vorozole </strong> JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 470 LP - 470 VL - 56 IS - supplement 3 AU - Anastasia Nikolopoulou AU - Yeona Kang AU - Paresh Kothari AU - Bin He AU - Shankar Vallabhajosula AU - Maria Figueiredo-Pereira AU - John Babich AU - Sophie Hurez Y1 - 2015/05/01 UR - http://jnm.snmjournals.org/content/56/supplement_3/470.abstract N2 - 470 Objectives It has been suggested that neuroinflammation (NI) is important to aggravation of brain damage and neurodegeneration (ND). Drug therapies to modulate NI hold promise to modulate ND. Recently, systemic inflammation has also emerged as a risk factor for ND. Administration of lipopolysaccharides (LPS) have been shown to trigger major brain inflammatory responses in the rat within 4-8h. Brain aromatase (an enzyme that converts androgens to estrogens) is thought to be involved in neuroprotection through the production of estradiol. To investigate the pathophysiologic importance of aromatase in the inflamed brain, we here report a µPET study with the radiolabeled aromatase inhibitor 11C-vorozole in LPS-treated rats.Methods Male Sprague-Dawley rats (270±50g) were intraperitoneally injected with a single dose of LPS from Salmonella enteriditis (10 mg/kg), in a volume of 0.3-0.4 mL. Animals were scanned using µPET and 11C-vorozole (37-74 MBq via tail vein) pre- and post- administration (at 24h) of LPS using a dynamic 60-min imaging protocol. Total volumes of distribution (Vt) of 11C-vorozole were calculated by kinetic modeling based on Logan plot with image-derived input function extracted from vena cava blood activity.Results After intravenous injection of 11C-vorozole, radioactivity accumulated in brain regions rich in aromatase expression such as the amygdala and the hypothalamus. LPS-treated rats showed significantly higher Vts than at baseline (1.56 ± 0.07 vs 1.11 ± 0.08 for amygdala; 1.38 ± 0.09 vs 0.97 ± 0.007 for hypothalamus) suggesting an upregulation of aromatase expression in inflamed rat brains.Conclusions In rat brains, LPS-induced systemic inflammation produces a robust increase in the aromatase expression levels that is readily detected with 11C-vorozole PET. 11C-vorozole PET may possibly provide critical information regarding the functional roles of aromatase in human inflammation and may be a useful probe for the study of neurodegenerative disorders.Research Support This investigation was supported by grant UL1TR000457 of the Clinical and Translation Sciences Center at Weill Cornell Medical College. ER -