Radiolabelled PD-L1 Inhibitor Monoclonal antibodies: Synthesis, Characterization and Validation

• Autor(a) principal: Fortunato, Maria Amaral Cabrita Ramalhão
• Data de Publicação: 2023
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/160352
• topic: Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Monoclonal antibodies have great potential for the treatment of cancer through Im-munotherapy. However, certain immunotherapies, like PD-L1 inhibitors, are dependent of specific biomolecule expression in tumour sites. Hence, biopsies followed by histochemistry are required, which are invasive and may be aggressive depending on the anatomical loca-tion of the tumour and not translate its anatomical-functional heterogeneity. In this regard, Nuclear Medicine imaging may provide alternative diagnostic means. Medically relevant radiometals have been utilized, such as the isotope 111In- emitting ɣ radiation, suitable for SPECT (Single-Photon Emission Computed Tomography) imaging. In this work, PD-L1 Inhibitor monoclonal antibodies, such as Atezolizumab (human) and its murine equivalent 6E11 were conjugated with a chelator DTPA which allowed to their labelling with the radionuclide 111In. From the resulting complexes, in vitro stability studies were performed in cell mediums, indicating that both conjugates remained stable with the radionuclide after 48 h. Flow cytometry and cellular uptake assays were also performed, resulting in high binding and cellular accumulation in high PD-L1 expressing cancer cells, which is indicative of the potential of these antibodies as imaging agents for PD-L1 expression.