A peptide receptor radionuclide therapy (PRRT) using [177Lu]/[90Y]-labeled somatostatin analogs has been proven to induce objective response in 30-45% of patients with advanced/progressive neuroendocrine tumors (NETs). 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 alpha-emitter-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]DOTA-TATOC. 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. Our Phase I Contract produced favorable results of the pre-clinical efficacy, long term-toxicity and dosimetry studies [212Pb]-octreotate. These results together with the safety, and dosimetry of 203Pb-octreotate in human allow us to propose the following objectives for the Phase II Contract: 1) Manufacturing of the clinical doses of [212Pb]-octreotate; (2) Initiation of Phase I dose escalation clinical studies of [212Pb]-octreotate in NETs patients. With success in these aims, we expect to a) evaluate our bussiness model of centralized production of clinical doses of [212Pb]-octreotate; b) assess the safety, and dose limiting toxicity of ascending doses of agent used for TAT of subjects with somatostatin receptor expressing NETs; c) determine the PK and the preliminary effectiveness of ascending doses of this drug.
