title: 11C-cetrozole: an improved C-11C-methylated PET probe for aromatase imaging in the brain.
abstract: 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, (11)C-cetrozole, which allows noninvasive quantification of aromatase expression.
  
  
  METHODS
  (11)C-cetrozole was synthesized by the C-(11)C-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.
  
  
  RESULTS
  In vitro and in vivo studies using (11)C-cetrozole showed its superiority in brain aromatase imaging in terms of specificity and selectivity, compared with previously developed (11)C-vorozole. PET studies showed that (11)C-cetrozole had a higher signal-to-noise ratio, providing a sharper image than (11)C-vorozole, because the radioactive metabolite of (11)C-vorozole was taken up into the brain. High specific binding of (11)C-cetrozole was observed in the amygdala and hypothalamus, and we also noted binding in the nucleus accumbens of rhesus monkeys for the first time.
  
  
  CONCLUSIONS
  These results suggest that PET imaging with newly developed (11)C-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.
authors.affiliation: RIKEN Center for Life Science Technologies, Hyogo, Japan.
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hosoya
authors.forename: Kayo
authors.initials: K
authors.lastname: Onoe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hiramatsu
authors.forename: Xiao-Le
authors.initials: XL
authors.lastname: Li
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takashima
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Onoe
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis*; D000818:Animals; D001141:Aromatase / Q000737:chemistry*; D047072:Aromatase Inhibitors / Q000737:chemistry; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D002250:Carbon Radioisotopes; D005260:Female; D020128:Inhibitory Concentration 50; D008253:Macaca mulatta; D008297:Male; D008745:Methylation; D049268:Positron-Emission Tomography; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000814:Aniline Compounds; D047072:Aromatase Inhibitors; D002250:Carbon Radioisotopes; D014230:Triazoles; C096486:YM 511; C000588985:cetrozole; C060523:vorozole; D001141:Aromatase
keywords: amygdala; aromatase; hypothalamus