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Auger electrons are known for their high linear energy transfer which can induce clustered DNA damage, leading to highly efficient cell death. Therefore, Auger electrons are ideal for attacking small metastatic tumors. In many cases, Auger electrons are typically emitted alongside other radiation such as gamma rays or positrons, which enable diagnostic imaging applications. Despite these advantages and years of research, only a limited number of radiopharmaceuticals using Auger emitters have been developed so far and only a few have reached clinical testing. This is largely due to the very short range of Auger electrons, which requires precise delivery of the emitters to critical cellular targets such as the nucleus.
In this study, we used ultra small gold nano-particles as carriers for the Auger emitter iodine-125 (125I) to create a new radiopharmaceutical.[1] After successful synthesis of nano-particles having less than 2 nm of diameter, the nano-carriers were radiolabeled with 125I. Radiolabeling yield was above 90 % and the stability remained above 95 % when tested in PBS for 72 hours. Cell studies in 2 D and 3D cell models showed low uptake as expected from literature but from the internalised particles around 30 % accumulated in the cell nucleus. This nucleus uptake proved to be sufficient to induce cell death even at low activities, i.e. 370 kBq, revealing the great potential of this approach. We have also shown that this approach can be extended to other Auger emitters such as 111In and other metallic nano-particles as longs as their size remains below 3 nm. Finally, we expect that the addition of tumour targeting vectors will improve the tumor-killing efficiency and we plan to investigate that in the future.
1. R. Wang, H. Liu, B, Antal, H, Th. Wolterbeek, A. G. Denkova, ACS Appl. Bio Mater. 2024, 7, 2, 1240–1249