Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m (99m Tc) and rhenium-188 (188 Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis (99m Tc: T 1/2 = 6 h, γ radiation = 140 keV) and therapy (188 Re: T 1/2 = 17 h, maximum β − energy = 2.12 MeV) and to their availability in the form of 99 Mo/ 99m Tc and 188 W/ 188 Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with 188 Re using two techniques: the direct labeling method [ 188 Re(V)] and the labeling method via the carbonyl nucleus [ 188 Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with 188 Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both 99m Tc and 188 Re were employed through 2 different procedures: (1) labeling of intact RTX with 99m Tc(I) and (2) reduced RTX (RTX red) labeled with 99m Tc(I)/ 188 Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method via carbonyl group, the results showed that the-SH groups of RTX red are a possible way of labeling. The formulation of 99m Tc(I)-RTX red was faster than 188 Re(I)-RTX red , that on the other hand showed better stability in human plasma and no transquelation in the cysteine or histidine challenge studies. Both compounds showed good binding affinity and a biodistribution in mice bearing tumor compatible with the normal mAb distribution and a reasonable tumor uptake proving the efficiency of the labeling and the potential clinical use. 5.4.4 Estudos in vivo: 99m Tc/ 188 Re(CO) 3-RTX red .
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