Abstract
Trastuzumab (Herceptin®), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. In this study, 188Re, an emitter with 2.12MeV β- and 0.155MeV γ and t1/2 = 16.9h, was labeled to trastuzumab aiming for radioimmunotherapy of HER2/neu-positive breast cancer. The 188Re(I)-tricarbonyl ion, [188Re(OH2)3(CO)3]+, was employed as a precursor for direct labeling 188Re to the monoclonal antibody. The resultant 188Re(I)-trastuzumab was found to be very stable even challenging with histidine. The tumor and normal tissues localization properties of 188Re(I)-trastuzumab in athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressing) and bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressing) were investigated. The in vivo biodistribution study demonstrated that 188Re(I)-trastuzumab was specifically accumulated in BT-474 tumor and the image of 188Re localized BT-474 tumor was clearly visualized within the useful lifetime of the radionuclide. By contrast, the 188Re(I)-trastuzumab uptakes in HER2-low expressing MCF-7 tumor was minimal so that the 188Re image localized at the tumor was not seen. It is revealed from the imaging study that 188Re(I)-trastuzumab may be a potential radioimmunotherapeutic agent for treatment of HER2/neu-overexpressing cancers.