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.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacokinetics , Antibodies, Monoclonal/pharmacokinetics , Antigens, Neoplasm/metabolism , Antineoplastic Agents/pharmacokinetics , Carcinoma/diagnostic imaging , Ovarian Neoplasms/diagnostic imaging , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal, Humanized/pharmacology , Antibody Affinity , Antibody Specificity , Antigens, Neoplasm/genetics , Antineoplastic Agents/pharmacology , Astatine/chemistry , Carcinoma/genetics , Carcinoma/immunology , Carcinoma/therapy , Cell Line, Tumor , Female , Gene Expression , Humans , Mice , Mice, Nude , Ovarian Neoplasms/genetics , Ovarian Neoplasms/immunology , Ovarian Neoplasms/therapy , Radioimmunotherapy , Radiopharmaceuticals/chemistry , Sodium-Phosphate Cotransporter Proteins, Type IIb/genetics , Sodium-Phosphate Cotransporter Proteins, Type IIb/metabolism , Technetium/chemistry , Tissue Distribution , Tomography, Emission-Computed, Single-Photon , Xenograft Model Antitumor AssaysABSTRACT
Piper tuberculatum, popularly known in Brazil as "jaborandi falso" and "pimenta darta", is widely used in folk medicine for the treatment of several diseases. In this study, the in vivo hollow fiber assay was used to investigate the antitumour efficacy of the crude extract and piplartine obtained from P. tuberculatum roots. Human glioblastoma (SF-295) and colon carcinoma (HCT-8) cell lines were used. In vitro cytotoxicity was assayed by the MTT assay. In the hollow fiber assay, nude mice implanted with tumour cells in hollow fibers were treated for four consecutive days via the intraperitoneal route, and tumour cell populations were assessed by the MTT assay. Both the crude extract and piplartine displayed cytotoxicity. In the hollow fiber assay, tumour growth inhibition rates were 24.6-54.8â% for the crude extract and 33.7-62.2â% for piplartine. No signal of toxicity was noticed. In conclusion, the crude extract and piplartine obtained from P. tuberculatum roots displayed in vitro and in vivo anticancer efficacy.
