Targeted Alpha Therapy with Thorium-227
Viviana Frantellizzi, Laura Cosma, Gabriele Brunotti, Arianna Pani, Angela Spanu, Susanna Nuvoli, Flaminia De Cristofaro, Liana Civitelli, Giuseppe De Vincentis
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 ( 223 Ra), 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 ( 227 Th) conjugates represent a new class of therapeutic radiopharmaceuticals for TAT. They are comprised of the α-emitter 227 Th 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 227 Th-labeled radioimmunoconjugates showed a relevant stability both in serum and vivo conditions with a significant antigen-dependent inhibition of cell growth. Unlike 223 Ra, the parent radionuclide 227 Th can form highly stable chelator complexes and is therefore amenable to targeted radioimmunotherapy. The authors discuss the future potential role of 227 Th TAT in the treatment of several solid as well as hematologic malignancies.