A peptide receptor radionuclide therapy (PRRT) using 177Lu/90Y-labeled somatostatin analogs have been proven to induce objective response in 30-45% of patients with advanced/progressive neuroendocrine tumors. The complete response to beta-emitter PRRT is rare. This is due to the fact that NETs are diagnosed at late stage of disease; the NETs patients with remissions could develop resistance to beta-radiation therapy that could be overcome by alphaemitter-targeted-therapy (TAT). The commercial potential of TAT has been confirmed by recent introduction of Xofigo for therapy of bone metastasis in prostate cancer; and remissions of NETs in patients undergoing therapy with [213Bi]DOTATOC and [225Ac]DOTATATOC. The TAT has a potential to revolutionize treatment of NETs whether applied alone or supported by beta-emitter PRRT. It can significantly enhance therapeutic efficacy of PRRT without side effects on non-targeted normal tissues. In the proposed research, we will determine the commercial feasibility of [212Pb]-octreotate. The objective of this Phase I SBIR is to: 1) Determine the feasibility of radiosynthesis of [212Pb]octreotate produced using AREVA Med high purity 212Pb generator; (2) Evaluate the pharmacokinetic, efficacy and toxicity of [212Pb]octreotate therapy in AR42J-xenographs; With success in these aims, we expect to advance our compound toward initiation of clinical studies and submission of NDA.
