Abstract
The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual ovarian cancer with 211At-Rebmab200. Here, the biodistribution of 211At-Rebmab200 was evaluated, as was the utility of 99mTc-Rebmab200 for bioimaging. Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we also assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors. Tumor antigen and cell binding were similar between Rebmab200 and murine MX35, as was biodistribution, including normal tissue uptake and in-vivo tumor binding. We also demonstrated that 99mTc-Rebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice. Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.
Highlights
Targeted alpha-particle therapy is a treatment modality that has gained interest for the adjuvant treatment of microscopic disseminated cancer due to the unique properties of alpha particles to deposit high energy at a cellular level
Rebmab200 was directly compared with its murine counterpart MX35 in terms of its in-vitro capacity for binding the immobilized NaPi2B epitope and live cells; we assessed its biodistribution in nude mice carrying subcutaneous OVCAR-3 tumors
We demonstrated that 99mTcRebmab200 can be used for single-photon emission computed tomography of subcutaneous ovarian carcinomas in tumor-bearing mice
Summary
Targeted alpha-particle therapy is a treatment modality that has gained interest for the adjuvant treatment of microscopic disseminated cancer due to the unique properties of alpha particles to deposit high energy at a cellular level. Among the limited set of possible α-emitting radionuclides, 211At is one of the most promising candidates. This radionuclide has been investigated in a number of preclinical studies that utilized the free halide [1] and various astatinated tumor-specific carrier vectors [2], the most common of which are monoclonal antibodies directed against a variety of malignancies [3,4,5]. Recurrences are primarily intra-abdominal along the peritoneal surface and are initially occult in the form of micrometastases. This scenario favors development of new local treatment strategies such as radioimmunotherapy
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