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Unique distribution of aromatase in the human brain: In vivo studies with PET and [ N ‐methyl‐ 11 C]vorozole
Author(s) -
Biegon Anat,
Kim Sung Won,
Alexoff David L.,
Jayne Millard,
Carter Pauline,
Hubbard Barbara,
King Payton,
Logan Jean,
Muench Lisa,
Pareto Deborah,
Schlyer David,
Shea Colleen,
Telang Frank,
Wang GeneJack,
Xu Youwen,
Fowler Joanna S.
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20791
Subject(s) - aromatase , letrozole , endocrinology , medicine , aromatase inhibitor , human brain , chemistry , psychology , neuroscience , breast cancer , cancer
Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [ N ‐methyl‐ 11 C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90‐min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V T ) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V T in all regions, though the size of the reduction was region‐dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage forthe noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain. Synapse 64:801–807, 2010. © 2010 Wiley‐Liss, Inc.