Physics Colloquium: "Targeted radionuclide therapy: the promise of short-lived alpha-emitting actinides" - Rebecca Abergel (UC Berkeley, Lawrence Berkeley National Laboratory)

Event Date

55 Roessler

Targeted alpha-particle therapy holds tremendous potential as a cancer treatment, since it offers the potential of delivering a highly cytotoxic dose to targeted cells while minimizing damage to the surrounding healthy tissue, due to the short range and high linear energy transfer of alpha particles. While the only available FDA-approved radioimmunoconjugates utilize beta-emitting isotopes, I-131, Y-90, and Lu-177, a few actinide isotopes have recently emerged as promising short-lived radionuclides that emit multiple α particles in their decay chains, dramatically increasing the potential delivered dose. In particular, Ac-225 and Th-227 can act as in vivo alpha-generator radionuclides and are of great interest for new therapeutic applications.

To create a targeted alpha therapeutic, one must assemble 3 basic parts: a targeting moiety, a radionuclide binding molecule, and an appropriate radionuclide such as Ac-225 or Th-227. Though sound in theory, and despite promising therapeutic potential established in pre-clinical and clinical studies, such designs have been slow to emerge. Reasons for this protracted development are many, including limited radioisotope supply, insufficient understanding of isotope biodistribution and biodosimetry, poor retention of alpha-emitting daughter products at the target site, as well as inadequate chelation, one of the major drawbacks.

To seek further development of Ac-225 and Th-227 bioconjugate therapeutics, ongoing efforts aim at addressing all of those limitations. Our approach to clearly delineate the coordination chemistry and biodistribution of these radioisotopes, their short-lived daughter products, resulting dosimetry, mechanisms of induced cellular toxicity, efficacy, and safety will be presented and discussed.

Part of the discussed work was supported by the U.S. Department of Energy’s Isotope Program in the Office of Nuclear Physics at the Lawrence Berkeley National Laboratory under Contract DE-AC02-05CH11231.