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Challenging production of Auger electron emitter platinum-195m via double-neutron capture activation of an iridium-193 target

Wawrowicz Kamil, Bilewicz Aleksander

Bio-Algorithms and Med-Systems

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2023

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Vol. 19, no. 1

35--39

EN

Targeted Auger electron (AE) therapy exhibits great potency against small tumors and metastatic sites, which to date have no effective therapeutic options. However, the development of AE-based therapy is significantly limited due to the low availability of the most promising radionuclides, being the consequence of the poor cognition of relevant nuclear pathways and insufficient accessibility of highly enriched target materials and specific infrastructure. Therefore, the development and investigation approaches to overcome this limitation are highly complex and challenging. In the present paper, as a second group worldwide, we perform experimental evaluation of double-neutron capture of a 195mPt production - radionuclide showing the most favourable characteristics for targeted Auger electron therapy. For this purpose we investigated two-step iridium target activation via 193Ir(n,γ) 194Ir(n,γ) 195mIr(β-)→195mPt. In presenting the current state of knowledge of identified production methods of this radionuclide, we highlight the limitations and challenges of cyclotron- and reactor-based approaches. With theoretical calculations followed by short-time irradiation with thermal neutron flux, we describe numerous nuclear and chemical difficulties associated with an investigated nuclear pathway. Obtained results reveal that research and commercial application of this method is significantly hindered or even impossible at the current state of knowledge. We point out the most critical limitations which need to be addressed for further consideration of the mentioned strategy. Therefore, 195mPt application for targeted Auger therapy still remains challenging and requires efforts to overcome the limitations.

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Radiobiokoniugaty znakowane emiterami elektronów Augera w celowanej terapii radionuklidowej

Wawrowicz Kamil, Bilewicz Aleksander

Wiadomości Chemiczne

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2020

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[Z] 74, 11-12

699--733

EN

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.

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Własności chemiczne pierwiastków transfermowych

Bilewicz Aleksander

Wiadomości Chemiczne

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1999

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[Z] 53, 9-10

631-645

EN

The chemical properties of transfermium elements are reviewed. The specific aspects of chemical operation with single atoms were briefly discussed. The chemical behaviour of mendelevium, nobelium and lawrencium is similar to that of the heaviest actinides. The only difference is the stabilization of +2 oxidation state in Md and No compounds. The chemical properties of the first three transactinide elements were compared with the properties of their lighter congeners in groups 4, 5 and 6 of the periodic table. The experimental results were compared with theoretical calculations. Special attention was paid to the influence of relativistic effects on the properties of the heaviest elements and their compounds.