title: Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.
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.
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Sture
authors.initials: S
authors.lastname: Lindegren
authors.affiliation: Recepta Biopharma, São Paulo, Brasil; Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Câncer do Estado de São Paulo, Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Luciana N S
authors.initials: LN
authors.lastname: Andrade
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Tom
authors.initials: T
authors.lastname: Bäck
authors.affiliation: Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Câncer do Estado de São Paulo, Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil; Laboratório de Investigação Médica Radioisótopos-LIM43, Departamento de Radiologiae Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Camila Maria L
authors.initials: CM
authors.lastname: Machado
authors.affiliation: Recepta Biopharma, São Paulo, Brasil.
authors.forename: Bruno Brasil
authors.initials: BB
authors.lastname: Horta
authors.affiliation: Laboratório de Investigação Médica Radioisótopos-LIM43, Departamento de Radiologiae Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Buchpiguel
authors.affiliation: Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, Brasil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Moro
authors.affiliation: Recepta Biopharma, São Paulo, Brasil; Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Oswaldo Keith
authors.initials: OK
authors.lastname: Okamoto
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Jacobsson
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Elin
authors.initials: E
authors.lastname: Cederkrantz
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Kohshin
authors.initials: K
authors.lastname: Washiyama
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Emma
authors.initials: E
authors.lastname: Aneheim
authors.affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.
authors.forename: Stig
authors.initials: S
authors.lastname: Palm
authors.affiliation: Cyclotron and PET Unit, KF-3982, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Holger
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Recepta Biopharma, São Paulo, Brasil.
authors.forename: Maria Carolina B
authors.initials: MC
authors.lastname: Tuma
authors.affiliation: Centro de Investigação Translacional em Oncologia (LIM24), Instituto do Câncer do Estado de São Paulo, Departamento de Radiologia e Oncologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.
authors.forename: Roger
authors.initials: R
authors.lastname: Chammas
authors.affiliation: Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg Sweden.
authors.forename: Ragnar
authors.initials: R
authors.lastname: Hultborn
authors.affiliation: Department of Oncology, Sahlgrenska Academy, University of Gothenburg, Gothenburg Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Albertsson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000493:pharmacokinetics* / Q000494:pharmacology; D000915:Antibody Affinity; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D001246:Astatine / Q000737:chemistry; D002277:Carcinoma / Q000000981:diagnostic imaging* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D045744:Cell Line, Tumor; D005260:Female; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000276:immunology / Q000628:therapy; D016499:Radioimmunotherapy; D019275:Radiopharmaceuticals / Q000737:chemistry; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb / Q000235:genetics / Q000378:metabolism; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D019275:Radiopharmaceuticals; C493557:SLC34A2 protein, human; D050614:Sodium-Phosphate Cotransporter Proteins, Type IIb; D013667:Technetium; D001246:Astatine