Targeted Alpha Therapy with Thorium-227

Abstract

Targeted alpha therapy (TAT) can deliver high localized burden of radiation selectively to cancer cells as well as the tumor microenvironment, while minimizing toxicity to normal surrounding cell. Radium-223 (²²³Ra), the first-in-class α-emitter approved for bone metastatic castration-resistant prostate cancer has shown the ability to prolong patient survival. Targeted Thorium-227 (²²⁷Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter ²²⁷Th complexed to a chelator conjugated to a tumor-targeting monoclonal antibody. In this review, the authors will focus out interest on this therapeutic agent. In recent studies ²²⁷Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike ²²³Ra, the parent radionuclide ²²⁷Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of ²²⁷Th TAT in the treatment of several solid as well as hematologic malignancies.

Keywords: cancer; radionuclide therapy; review; targeted therapy; thorium-227; α-emitter.