Alpha Emitters — Decay Chains, Chelation Chemistry & Radiopharmaceuticals — An Overview

Abstract: The development of targeted α-particle therapy (TAT) holds ample promise in treating radiation-, immunotherapy-, and chemo-resistant cancers or diseases with no alternative treatment options. Αlpha-particles are approximately 8,000 times more massive than β-particles, with a limited range of 50–100 μm and a high linear energy transfer (LET) with a mean energy deposition of 100 keV/μm, which partially explains their effectiveness. However, there seems to be much more to TAT, especially when exploring the connection of TAT and the abscopal or other off-targeted effects.

Due to its first clinical success stories, the field of TAT has grown enormously within the last two decades, and its current state might appear complex yet overwhelming. A brief refresher of the TAT basics, challenges, and selected novel highlights might be appreciated. This presentation provides a broad overview of the work with α-emitting nuclides — starting with their availability and concluding with their employment in preclinical studies. Emphasis will be put on radionuclides with ‘complex’ decay chains (e.g., actinium-225 & lead-212), the fate of their progeny, and their physical and chemical properties. Touching briefly on the challenges of finding a theranostics match (an imaging-compatible radionuclide) — this talk focuses on matching the available radionuclides to the most suitable delivery systems and targets. Here, one highlight will be a short detour to explore the feasibility and potential benefits of in vivo bioorthogonal click chemistry — also known as the ‘pretargeting strategy’.

Ultimately, this refresher will have prepared the listener, with the necessary chemical, physical, and preclinical background, to dive into more complex adventures of cutting-edge TAT developments deliberately.