Marshalling the Potential of Auger Electron Radiopharmaceutical Therapy

Abstract

Auger electron (AE) radiopharmaceutical therapy (RPT) may have the same therapeutic efficacy as α-particles for oncologic small disease, with lower risks of normal-tissue toxicity. The seeds of using AE emitters for RPT were planted several decades ago. Much knowledge has been gathered about the potency of the biologic effects caused by the intense shower of these low-energy AEs. Given their short range, AEs deposit much of their energy in the immediate vicinity of their site of decay. However, the promise of AE RPT has not yet been realized, with few agents evaluated in clinical trials and none becoming part of routine treatment so far. Instigated by the 2022 "Technical Meeting on Auger Electron Emitters for Radiopharmaceutical Developments" at the International Atomic Energy Agency, this review presents the current status of AE RPT based on the discussions by experts in the field. A scoring system was applied to illustrate hurdles in the development of AE RPT, and we present a selected list of well-studied and emerging AE-emitting radionuclides. Based on the number of AEs and other emissions, physical half-life, radionuclide production, radiochemical approaches, dosimetry, and vector availability, recommendations are put forward to enhance and impact future efforts in AE RPT research.

Keywords: Auger electrons emitters; radiopharmaceutical therapy; radiopharmaceuticals; recommendations.

Graphical abstract

FIGURE 1.

Range, cross irradiation, and ionization patterns of β, α, and AE on scale of tumor/tumor cells (upper left) and DNA (lower left). Emission of Auger and conversion electrons after electron capture and internal conversion (right). IC = internal conversion.

FIGURE 2.

Although nucleus and DNA are typically the primary cellular targets of radiation damage, internalization into cancer cells and delivery to cell nucleus is not required for cell killing with AE-emitting radionuclides. Targeting of cell membrane can be an effective strategy for killing cancer cells with AEs (18). AEs can also initiate strong bystander response that significantly participates in cell killing (23,29,30).

FIGURE 3.

Overall dosimetry score for radionuclides for AE RPT: unfavorable (10–26), somewhat favorable (26–41), favorable (41–56), and highly favorable (≥55).