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.