TY - JOUR T1 - <em>In vivo</em> distribution of human brain aromatase with [<sup>11</sup>C]vorozole JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 103 LP - 103 VL - 51 IS - supplement 2 AU - Anat Biegon AU - Sung Won Kim AU - Jean Logan AU - David Schlyer AU - Frank Telang AU - Gene-Jack Wang AU - Joanna Fowler Y1 - 2010/05/01 UR - http://jnm.snmjournals.org/content/51/supplement_2/103.abstract N2 - 103 Objectives Aromatase (Cyp19A) catalyzes the last step in estrogen biosynthesis. It is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition and neuroprotection. We recently developed a purification method to separate [11C]vorozole, a specific aromatase tracer, from other labeled isomers (Kim et al, 2009). Here we characterized the distribution and kinetics of [11C]vorozole in human subjects using positron emission tomography (PET). Methods Six young, healthy subjects, 3 men and 3 women, were administered [11C]vorozole (&gt;10 mCi/nmole, 2.99-7.43 mCi) on two separate occasions. Specificity was confirmed by pretreatment with a pharmacological dose of the aromatase inhibitor, letrozole (2.5 mg). PET data were acquired over a 90 min session and regions of interest were placed over selected brain regions. Brain and plasma time activity data were used to calculate the distribution volume (VT). Results Time activity curves revealed fast penetration into the brain followed by rapid clearance and then selective accumulation and retention by brain regions such as thalamus and amygdala. At 1 hr post injection, 60 % of plasma radioactivity was [11C]vorozole. VT values in both men and women followed the rank order: thalamus &gt; amygdala = preoptic area &gt; medulla (inferior olive) &gt; accumbens, pons, occipital and temporal cortex, putamen, cerebellum and white matter. Pretreatment with letrozole reduced VT in all regions. Conclusions The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the non-invasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain and in drug R&amp;D. Research Support NIAAA, NIDA and DOE-OBER (infrastructure) ER -