Tocilizumab Labeling with 99mTechnetium via HYNIC as a Molecular Diagnostic Agent for Multiple Myeloma

Author(s): Ximena Camacho, Camila Longo Machado, Maria Fernanda García, Marcelo Fernández, Natalia Oddone, Juan Benech, Juan Pablo Gambini, Hugo Cerecetto, Roger Chammas, Pablo Cabral, Eloisa Riva*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 9 , 2017

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Graphical 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 99mTechnetium 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 99mTc. 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 99mTc- HYNIC-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.

Keywords: Tocilizumab, IL-6R, 99mTc-HYNIC-tocilizumab, molecular imaging, multiple myeloma.

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Article Details

Year: 2017
Page: [1267 - 1277]
Pages: 11
DOI: 10.2174/1871520617666170213144917
Price: $65

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