title: PET of aromatase in gastric parietal cells using 11C-vorozole.
abstract: Aromatase is a rate-limiting enzyme for estrogen biosynthesis and has been implicated in pathophysiological states of various diseases via estrogen production. This enzyme is known to be widely distributed in extragonadal and gonadal tissues including the stomach. In contrast to circulating estrogen, the functional role of gastric aromatase/estrogen has not been elucidated in detail, because there is no efficient methodology to investigate spatiotemporal changes of gastric aromatase/estrogen in vivo. Recently, (S)-(11)C-6-[(4-chlorophenyl)(1H-1,2,4-triazole-1-yl)methyl]-1-methyl-1H-benzotriazole ((11)C-labeled vorozole), based on a potent nonsteroidal aromatase inhibitor, has been developed as a tracer to investigate aromatase distribution in living animals and humans using a noninvasive PET technique. In the present study, we investigated gastric aromatase expression by means of PET with (11)C-vorozole.
  
  
  METHODS
  After bolus injection of (11)C-vorozole into the tail vein, emission scans were obtained for 90 min on male and female rats under isoflurane anesthesia. Displacement studies with unlabeled vorozole and autoradiographic analysis were conducted for demonstration of specific binding. Immunohistochemistry was performed to confirm aromatase expression.
  
  
  RESULTS
  PET scans revealed that (11)C-vorozole highly accumulated in the stomach and adrenal glands. Displacement studies and autoradiography demonstrated that aromatase was expressed in the stomach but that the accumulation of (11)C-vorozole in the adrenal glands might be through nonspecific binding. Immunohistochemical analysis revealed that aromatase is expressed in gastric parietal cells but not in adrenal glands. Moreover, the accumulation of (11)C-vorozole in the stomach was significantly increased in fatigued rats.
  
  
  CONCLUSIONS
  These results suggest that the (11)C-vorozole PET technique is a useful tool for evaluation of gastric aromatase dynamics in vivo, which may provide important information for understanding the molecular mechanisms of gastric aromatase/estrogen-related pathophysiological processes and for the development of new drugs.
authors.affiliation: Molecular Probe Dynamics Laboratory, RIKEN Center for Molecular Imaging Science, Minatojima minamimachi, Chuo-ku, Kobe, Hyogo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Ozawa
authors.forename: Kayo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Ko-Hei
authors.initials: KH
authors.lastname: Akazawa
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Takashima
authors.forename: Hiroko
authors.initials: H
authors.lastname: Nagata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Doi
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Hosoya
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Yilong
authors.initials: Y
authors.lastname: Cui
authors.forename: Yosky
authors.initials: Y
authors.lastname: Kataoka
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001345:Autoradiography; D002250:Carbon Radioisotopes; D005221:Fatigue / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D010295:Parietal Cells, Gastric / Q000000981:diagnostic imaging* / Q000201:enzymology* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles; D051598:Whole Body Imaging
chemical_list: D002250:Carbon Radioisotopes; D014230:Triazoles; C060523:vorozole; D001141:Aromatase