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https://observatorio.fm.usp.br/handle/OPI/21856
Title: | Tocilizumab Labeling with (99m)Technetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma |
Authors: | CAMACHO, Ximena; MACHADO, Camila Longo; GARCIA, Maria Fernanda; FERNANDEZ, Marcelo; ODDONE, Natalia; BENECH, Juan; GAMBINI, Juan Pablo; CERECETTO, Hugo; CHAMMAS, Roger; CABRALA, Pablo; RIVA, Eloisa |
Citation: | ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, v.17, n.9, p.1267-1277, 2017 |
Abstract: | Background: Multiple myeloma is the second most common hematological malignancy. Interleukin-6 (IL-6) is one of the key molecules related to growth, survival and proliferation of myeloma cells. Tocilizumab is a humanized monoclonal antibody directed against receptor of IL-6. Objective: To radiolabel Tocilizumab with (99m)Technetium as a potential imaging agents for MM. Methods: IL-6R expression was studied by laser confocal microscopy in MM cell lines (U266, NCI-H929 and MM1S). Tocilizumab was derivatized with NHS-HYNIC-Tfa and radiolabeling with Tc-99m. Radiochemical stability was determined. In-vitro binding and immunoreactive fraction assays were performed. Biodistribution and SPECT/CT imaging were evaluated in healthy BALB/c and MM-bearing BALB/c nude mice. Results: LCM studies allowed us to demonstrate that U266, NCI-H929 and MM1S cells present high expression of IL-6R in cell membrane. Radiolabeling was carried out in a fast, reproducible, easy and stable way having high radiochemical purity and did not interfere with epitope recognition. The immunoreactive fraction of (TcHYNIC)-Tc-99m-Tocilizumab was 86.35%. Biodistribution showed a high uptake in liver, spleen, gastrointestinal tract and kidneys. SPECT/CT imaging of MM-bearing BALB/c nude mice showed liver uptake and a high tumor selective uptake at 24 hours. Conclusions: Our results support the potential role of 99mTc-HYNIC-Tocilizumb as a novel MM radiotracer for targeting IL-6 expression in-vivo. We describe the development of a formulation kit to radiolabeling monoclonal antibodies in a clinical setting. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for MM disease. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MDR Artigos e Materiais de Revistas Científicas - LIM/24 Artigos e Materiais de Revistas Científicas - LIM/43 Artigos e Materiais de Revistas Científicas - ODS/03 |
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