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

Abstract Introduction Sigma receptors are overexpressed in a variety of human tumors, making them potential targets for radionuclide receptor therapy. We have previously synthesized and evaluated131 I-labeled (+)-2-[4-(4-iodophenyl)piperidino]cyclohexanol [(+)-[131 I] p IV], which has a high affinity for sigma receptors. Therefore, (+)-[131 I] p IV 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 (+)-[211 At] p AtV, an211 At-labeled sigma receptor ligand, that has potential use in alpha-radionuclide receptor therapy. Methods The radiolabeled sigma receptor ligand (+)-[211 At] p AtV was prepared using a standard halogenation reaction generating a 91% radiochemical yield with 98% purity after HPLC purification. The partition coefficient of (+)-[211 At] p AtV was measured. Cellular uptake experiments and in vivo biodistribution experiments were performed using a mixed solution of (+)-[211 At] p AtV and (+)-[125 I] p IV; the human prostate cancer cell line DU-145, which expresses high levels of the sigma receptors, and DU-145 tumor-bearing mice. Results The lipophilicity of (+)-[211 At] p AtV was similar to that of (+)-[125 I] p IV. DU-145 cellular uptake and the biodistribution patterns in DU-145 tumor-bearing mice at 1 h post-injection were also similar between (+)-[211 At] p AtV and (+)-[125 I] p IV. Namely, (+)-[211 At] p AtV demonstrated high uptake and retention in tumor via binding to sigma receptors. Conclusion These results indicate that (+)-[211 At] p AtV could function as an new agent for alpha-radionuclide receptor therapy.