sup 11^C-Cetrozole: An Improved C-^sup 11^C-Methylated PET Probe for Aromatase Imaging in the Brain

Aromatase (an enzyme that converts androgens to estrogens) in the brain is involved in neuroprotection, synaptic plasticity, and regulation of sexual and emotional behaviors. To investigate the physiologic and pathologic importance of aromatase in the brain, including in humans, we here report the development of a novel PET probe for aromatase, 11C-cetrozole, which allows noninvasive quantification of aromatase expression. 11C-cetrozole was synthesized by the C-11C-methylation method developed by our group. In vitro autoradiography of frozen sections and a binding study with rat brain homogenates were conducted to demonstrate the specific binding and the dissociation constant. PET studies with anesthetized rhesus monkeys were performed to analyze the dynamics in the brain. In vitro and in vivo studies using 11C-cetrozole showed its superiority in brain aromatase imaging in terms of specificity and selectivity, compared with previously developed 11C-vorozole. PET studies showed that 11C-cetrozole had a higher signal-to-noise ratio, providing a sharper image than 11C-vorozole, because the radioactive metabolite of 11C-vorozole was taken up into the brain. High specific binding of 11C-cetrozole was observed in the amygdala and hypothalamus, and we also noted binding in the nucleus accumbens of rhesus monkeys for the first time. These results suggest that PET imaging with newly developed 11C-cetrozole is suitable for quantifying the expression of brain aromatase in vivo, possibly providing critical information regarding the functional roles of aromatase in human neurologic and emotional disorders.