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

IntroductionSigma receptors are overexpressed in a variety of human tumors, making them potential targets for radionuclide receptor therapy. We have previously synthesized and evaluated 131I-labeled (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[131I]pIV], which has a high affinity for sigma receptors. Therefore, (+)-[131I]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 (+)-[211At]pAtV, an 211At-labeled sigma receptor ligand, that has potential use in alpha-radionuclide receptor therapy.MethodsThe radiolabeled sigma receptor ligand (+)-[211At]pAtV was prepared using a standard halogenation reaction generating a 91% radiochemical yield with 98% purity after HPLC purification. The partition coefficient of (+)-[211At]pAtV was measured. Cellular uptake experiments and in vivo biodistribution experiments were performed using a mixed solution of (+)-[211At]pAtV and (+)-[125I]pIV; the human prostate cancer cell line DU-145, which expresses high levels of the sigma receptors, and DU-145 tumor-bearing mice.ResultsThe lipophilicity of (+)-[211At]pAtV was similar to that of (+)-[125I]pIV. DU-145 cellular uptake and the biodistribution patterns in DU-145 tumor-bearing mice at 1 h post-injection were also similar between (+)-[211At]pAtV and (+)-[125I]pIV. Namely, (+)-[211At]pAtV demonstrated high uptake and retention in tumor via binding to sigma receptors.ConclusionThese results indicate that (+)-[211At]pAtV could function as an new agent for alpha-radionuclide receptor therapy.