An approach to assessing the contribution of the high LET effect in strategies for Auger endoradiotherapy. (2nd January 2023)

• Record Type: Journal Article
• Authors: Lobachevsky, Pavel; Skene, Colin; Munforte, Laura; Smith, Andrea; White, Jonathan; Martin, Roger F.
• Is Part Of: International journal of radiation biology. Volume 99:Number 1(2023)
• Page Start: 95
• Page End: 102
• Publication Date: 2023-01-02
• Subjects: Auger emitters -- high LET -- DNA damage -- DNA-binding radioprotectors; Radiation -- Physiological effect -- Periodicals; Radiobiology -- Periodicals; 571.45
• DOI: 10.1080/09553002.2021.1976862
• Languages: English
• ISSNs: 0955-3002

Abstract

Abstract: Purpose: The interest in exploiting Auger emitters in cancer therapy stems from their high linear energy transfer (LET)-type radiation damage to DNA. However, the design of Auger-emitter labeled vehicles that target the Auger cascade specifically to the DNA of tumour cells is challenging. Here we suggest a possible approach to evaluate tumour-targeting Auger-labeled conjugates by assessing the impact of a radioprotector known to be effective in protecting from low LET radiation, but not high LET radiation. Given some similarity between the energy spectrum of Auger electrons and that of secondary electrons from soft X-rays, we report the results of radioprotection experiments with 25 kVp X-rays. Materials and methods: Clonogenic survival curves for cultured human keratinocytes were established for three different irradiation conditions: 137 Cs γ-rays, 25 kVp X-rays and 320 kVp X-rays, and the effect of including a new radioprotector, denoted "2PH", was investigated. Results: The extent of radioprotection by 2PH was comparable for all radiation conditions, although RBE was higher (about 1.7) for soft X-rays. Conclusions: Radioprotectors like 2PH will help to evaluate Auger endoradiotherapy strategies, by determining the relative contributions of the high-LET effects (not protected), compared to other components, such as Auger electrons not effectively targeted to DNA.