99mTc-Tocilizumab a new molecular imaging agent for in Multiple Myeloma.
DOI:
https://doi.org/10.35954/SM2012.31.1.2Keywords:
Hynic; Multiple Myeloma; Tocilizumab, IL-6 RECL; iL-6 Family Cytokyne; Tricarbonyl.Abstract
Interleukin-6 (IL-6) is a key molecule in the pathogenesis of multiple myeloma (MM). Over-expression of its receptor, IL6R, in MM cells can be used as a target for the development of potential molecular agents for its diagnosis. Tocilizumab (Actemra®) is a monoclonal antibody against IL6R.
The objective of this work is to develop and evaluate, through different chemical and biological methods, the labeling of 99mTc-Tocilizumab using two chelating agents, Succidinimyl-hydrazinonicotinamide (HYNIC) and tricarbonyl.
Tocilizumab (Roche) was first derivatized with HYNIC and labeled using 99mTc/tricine/Sn2Cl at room temperature. Antibody labeling with [99mTc(CO)3(OH2)3]+ was carried out by incubating 45 min at 37°C. Radiochemical purity (PQR) was evaluated by ITLC-SG and HPLC. In-vitro binding and competition studies were performed with MM U266 cells for up to 120 min. Fluorescent and atomic force microscopy images of U266 cells were obtained. In-vivo studies were performed in normal CD1 mice (n=3).
A PRQ greater than 90% was observed with both chelators used, being stable and showing no significant transchelation for at least 24 hs. Confocal microscopy showed the ability of Tocilizumab-FITC to recognize IL6R in U266 cells. In-vitro binding and displacement experiments confirm the specificity of recognition of 99mTc-Tocilizumab by IL6R. Biodistribution studies showed hepatic absorption and renal elimination mainly.
From the results obtained it was concluded that both 99mTco4- labeled Tocilizumab, via HYNIC and via tricarbonyl, could be potential imaging agents for the diagnosis of Multiple Myeloma.
Received for review: June 2012.
Accepted for publication: August 2012.
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