Development of therapeutic radiopharmaceuticals labeled with novel beta-emitting radionuclide

Abstract

  Copper-67 is an attractive radionuclide for nuclear medicine therapy, which has an emitted β-particle energy suitable to penetrate small tumors and a physical half-life of 61.8 hours long enough for ⁶⁷Cu-labeled ligands to accumulate at tumor sites. Recently, radioimmunotherapy (RIT) becomes one of the most promising treatments for cancer therapy. High energy β-particle-emitting ⁹⁰Y (2.28MeV) becomes available for clinical use and shows high efficacy, but its application is limited by adverse effects. ⁶⁷Cu has middle energy β-particles (0.39 – 0.58MeV), and its maximal tolerated activity dose is much higher than ⁹⁰Y. So, ⁶⁷Cu may have an advantage in treating relatively small tumor masses. Additionally, various agents to deliver copper radionuclides to tumors have been investigated and copper-diacetyl-bis(N⁴-methylthiosemicarbazone) (Cu-ATSM) shows the ability of delivering copper radionuclides to tumors under hypoxic condition. We prepared a newly developed radiopharmaceuticals labeled with ⁶⁷Cu, and evaluated its potential for treatment of cancer in mice. In this study, we are successfully prepared a high affinity CD20-specific monoclonal antibody (mAb). ⁶⁷Cu-TETA-NuB2 was high accumulated to CD20+ tumor, so it was expected to be suitable for treatment of non-Hodgkin’s B-cell lymphoma. The use of ⁶⁷Cu for RIT has potential for efficient tailor-made therapy.