Auger: The future of precision medicine

Abstract

First reported by Lise Meitner in 1922 and independently by Pierre Auger in 1923, the Auger effect has been explored as a potential source for targeted radiotherapy. The Auger effect is based on the emission of a low energy electron (typically <25 keV) from an atom post electron capture (EC), internal conversion (IC), or incident X-rays excitation. This phenomenon can cause the emission of a primary electron and multiple electron tracks typically in the nearest proximity of the emission site (2-500 nm). The short range of the emitted Auger cascade results in medium/high levels of linear energy transfer (4-26 keV/μm) exerted on the surrounding tissue. This property makes Auger emitters the ideal candidates for delivering high levels of targeted radiation to a specific target with dimensions comparable to, for example, the DNA. By using a targeting vector such as a small molecule, peptide or antibody, one has the potential of delivering high levels of radiation to tumor specific biomarkers while circumventing off-site toxicity in healthy cells; a challenge which is harder to overcome when using other, longer range sources of radiation such as beta and alpha emitting radionuclides. Several reviews on Auger emitters have been published over the years with two recent examples. For these reviews and others, we support their analysis and therefore to avoid simple repetition, this commentary will seek to address additional aspects and viewpoints. Specifically, we will focus on those most promising preclinical and clinical studies using small molecules, peptides, antibodies and how these studies may serve as a template for future studies.

Figure1.. Auger radiotherapy.

A. Potential carriers of Auger radiation emitting nuclides for cancer therapy have included small molecules ([¹²⁵I]UdR [16], [¹²³I]I-MAPi [17], [¹²⁵I]DCIBzL[18]), nanoparticles, and monoclonal antibodies. B. Timeline of select clinical trials using Auger radiotherapy since their discovery in 1922/1923.