title: Evaluation of radioiodinated 1-[2-(3,4-Dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine as a tumor diagnostic agent with functional sigma receptor imaging by single photon emission computed tomography.
abstract: Radioiodinated 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine (o-BON) and 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-iodophenylpropyl)piperazine (m-BON) were evaluated as single photon emission computed tomography (SPECT) radiopharmaceuticals for tumor imaging by visualization of sigma receptors. In vivo biodistribution studies of [125 I]o-BON and [125 I]m-BON in tumor-bearing mice showed a high tumor uptake and prolonged retention of radiolabeled compounds in the tumor. In contrast with these factors, the blood and muscle accumulations were low, which resulted in a good tumor-to-blood ratio and tumor-to-muscle ratio. In peripheral organs, [125 I]o-BON showed rapid clearance in comparison with [125 I]m-BON. Selective interactions of [125 I]o-BON and [125 I]m-BON with sigma receptors on tumor cell membranes were confirmed by pretreatment experiments with various sigma and other receptor ligands. [125 I]o-BON possesses higher specific binding toward sigma receptors than does [125 I]m-BON; thus, [125 I]o-BON was chosen for further evaluations. High uptake of [125 I]o-BON was observed in various tumors, and a good linear correlation (R2=0.70) was found between accumulation of [125 I]o-BON and the sigma receptor expression level. Furthermore, the accumulation of [125 I]o-BON in tumors reflected their proliferation rate. These results suggest that it is feasible to use radioiodinated o-BON as a marker for measuring the proliferative status associated with sigma receptor expression.
authors.affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. hirata@gly.oups.ac.jp
authors.forename: Masahiko
authors.initials: M
authors.lastname: Hirata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mori
authors.forename: Takuya
authors.initials: T
authors.lastname: Umeda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Abe
authors.forename: Tomoya
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Ohmomo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010879:Piperazines / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017480:Receptors, sigma / Q000187:drug effects*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: C515064:1-(2-(3,4-dimethoxyphenyl)ethyl)-4-(3-(3-iodophenyl)propyl)piperazine; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D017480:Receptors, sigma