In Vivo Imaging of Brain Aromatase in Female Baboons: [C]Vorozole Kinetics and Effect of the Menstrual Cycle

Abstract

The aim of this work was to quantify the brain distribution of the enzyme aromatase in the female baboon with positron emission tomography and the tracer [ 11 C]vorozole using three different quantification methods for estimating the total distribution volume (V T ): a graphical method, compartment modeling, and a tissue to plasma ratio. The graphical model and the compartment modeling gave similar estimates to the data and similar values (correlation R = .988; p = .0001). [ 11 C]Vorozole shows a rapid uptake by the brain followed by a relatively constant accumulation, suggesting the possibility of using the tissue to plasma ratio as an estimate of V T . The highest uptake of [ 11 C]vorozole in the baboon brain was measured in the amygdala, followed by the preoptic area and hypothalamus, basal ganglia, and cortical areas. Pretreatment studies with vorozole or letrozole showed a generalized decrease in brain accumulation and V T . The results suggested that the physiologic changes in gonadal hormone levels accompanying the menstrual cycle had a significant effect on brain aromatase V T .