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Radiobiokoniugaty znakowane emiterami elektronów Augera w celowanej terapii radionuklidowej

Wawrowicz Kamil, Bilewicz Aleksander

Wiadomości Chemiczne

2020

[Z] 74, 11-12

699--733

In contrast to the radiation therapy methods, that use an external ion beam source, the internal radiotherapy is performed by the direct administration of radionuclides conjugated to a targeting vector. Crucial criteria for the use of radiopharmaceuticals at a selective localization and retention in the tumor lesion are biological or biochemical differences between tumor and non-tumor tissue. Auger electron emitters that can target cancer cells are an attractive agents for internal radiation therapy. Besides of a emitters, radionuclides that decay with the emission of very low energy Auger electrons are well suited for the treatment of small tumors, micrometastases or residual tumor after surgical resection of a primary lesion. In contrast to a radiation, however, Auger emitters have low toxicity when decaying outside the cell during blood transport and they are therefore interesting candidates for targeted radionuclide therapy. However, due to nanometers range of Auger electrons the challenge is to target cancer cells specifically and achieve intracellular and intranuclear uptake for maximum DNA damage. So far, no system has been developed to allow for selective delivery of the Auger electron emitter to the cancer cell and next delivering it to cell nucleus, near the DNA strand. An overview of Auger radiation therapy approaches of the past decade shows several research directions and various targeting vehicles. The latter include small molecules, aptamers, hormones, halogenated nucleotides, peptides oligonucleotides and monoclonal antibodies and their fragments. In present article we discuss the basic principles of Auger electron therapy as compared with targeted α and β radionuclide therapy, characteristic of used Auger emitters and briefly the main advantages and disadvantages of the different targeting modalities that are under investigation.