Preparation and evaluation of an astatine-211-labeled sigma receptor ligand for radionuclide therapy

Ogawa, Kazuma*; Mizuno, Yoshiaki*; Washiyama, Koshin*; Shiba, Kazuhiro*; Takahashi, Naruto*; Kozaka, Takashi*; Watanabe, Shigeki; Shinohara, Atsushi*; Odani, Akira*

Sigma receptors are overexpressed in a variety of human tumors, making them potential targets for radionuclide receptor therapy. We have previously synthesized and evaluated I-labeled (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[I]pIV], which has a high affinity for sigma receptors. Therefore, (+)-[I]pIV significantly inhibited tumor cell proliferation in tumor-bearing mice. In the present study, we report the synthesis and the in vitro and in vivo characterization of (+)-[At]pAtV, an At-labeled sigma receptor ligand, that has potential use in -radionuclide receptor therapy. The lipophilicity of (+)-[At]pAtV was similar to that of (+)-[I]-pIV. Uptake of DU-145, prostate cancer cell lines, and the biodistribution patterns in DU-145 tumor-bearing mice at 1 h post-injection were also similar between (+)-[At]pAtV and (+)-[I]-pIV. Namely, (+)-[At]pAtV demonstrated high uptake and retention in tumor via binding to sigma receptors.