title: Development and evaluation of a radiobromine-labeled sigma ligand for tumor imaging.
abstract: BACKGROUND
  Sigma receptors are appropriate targets for tumor imaging because they are highly expressed in a variety of human tumors. Previously, we synthesized a vesamicol analog, (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol ((+)-pIV), with high affinity for sigma receptors, and prepared radioiodinated (+)-pIV. In this study, to develop a radiobromine-labeled vesamicol analog as a sigma receptor imaging agent for PET, nonradioactive and radiobromine-labeled (+)-2-[4-(4-bromophenyl)piperidino]cyclohexanol ((+)-pBrV) was prepared and evaluated in vitro and in vivo. In these initial studies, (77)Br was used because of its longer half-life.
  
  
  METHODS
  (+)-[(77)Br]pBrV was prepared by a bromodestannylation reaction with radiochemical purity of 98.8% after HPLC purification. The partition coefficient of (+)-[(77)Br]pBrV was measured. In vitro binding characteristics of (+)-pBrV to sigma receptors were assayed. Biodistribution experiments were performed by intravenous administration of a mixed solution of (+)-[(77)Br]pBrV and (+)-[(125)I]pIV into DU-145 tumor-bearing mice.
  
  
  RESULTS
  The lipophilicity of (+)-[(77)Br]pBrV was lower than that of (+)-[(125)I]pIV. As a result of in vitro binding assay to sigma receptors, the affinities of (+)-pBrV to sigma receptors were competitive to those of (+)-pIV. In biodistribution experiments, (+)-[(77)Br]pBrV and (+)-[(125)I]pIV showed high uptake in tumor via sigma receptors. The biodistributions of both radiotracers showed similar patterns. However, the accumulation of radioactivity in liver after injection of (+)-[(77)Br]pBrV was significantly lower compared to that of (+)-[(125)I]pIV.
  
  
  CONCLUSIONS
  These results indicate that radiobromine-labeled pBrV possesses great potential as a sigma receptor imaging agent for PET.
authors.affiliation: Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. kogawa@p.kanazawa-u.ac.jp
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ogawa
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kanbara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kiyono
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Tatsuto
authors.initials: T
authors.lastname: Kiwada
authors.forename: Takashi
authors.initials: T
authors.lastname: Kozaka
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiba
authors.forename: Akira
authors.initials: A
authors.lastname: Odani
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001692:Biological Transport; D001967:Bromine Radioisotopes; D045744:Cell Line, Tumor; D003511:Cyclohexanols / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D015195:Drug Design; D006801:Humans; D007553:Isotope Labeling; D008024:Ligands; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D017480:Receptors, sigma / Q000378:metabolism*
chemical_list: D001967:Bromine Radioisotopes; D003511:Cyclohexanols; D008024:Ligands; D017480:Receptors, sigma