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Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.

Lindegren S, Andrade LN, Bäck T, Machado CM, Horta BB, Buchpiguel C, Moro AM, Okamoto OK, Jacobsson L, Cederkrantz E, Washiyama K, Aneheim E, Palm S, Jensen H, Tuma MC, Chammas R, Hultborn R, Albertsson P - PLoS ONE (2015)

Bottom Line: 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.Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus

Tissue distributions of 211At-MX35 and 211At-Rebmab200.211At-MX35 (filled bars) and 211At-Rebmab200 (open bars). Results are given as mean ± standard deviation of percent injected activity per gram tissue (%-IA/g). *P<0.05 by Student’s t-test. Abbreviation RBM L&R is the red bone marrow taken from left and right femur.
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pone.0126298.g003: Tissue distributions of 211At-MX35 and 211At-Rebmab200.211At-MX35 (filled bars) and 211At-Rebmab200 (open bars). Results are given as mean ± standard deviation of percent injected activity per gram tissue (%-IA/g). *P<0.05 by Student’s t-test. Abbreviation RBM L&R is the red bone marrow taken from left and right femur.

Mentions: The distribution results were cross-evaluated; the biodistribution of 211At-MX35 was compared with that of 211At-Rebmab200 (Fig 3), and the biodistribution of 125I-MX35 was compared with that of 125I-Rebmab200 (Fig 4). There were no or only minor differences between humanized and murine MX35. A significant difference (P<0.05) was associated with a slightly lower retention in the blood of 211At-Rebmab200-treated mice versus mice treated with 211At-MX35 (Fig 3). There was also higher uptake in the throat (thyroid) of free 125I than 211At (Fig 4), indicating that conjugated astatinated antibodies were more stable than directly iodinated antibodies.


Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200.

Lindegren S, Andrade LN, Bäck T, Machado CM, Horta BB, Buchpiguel C, Moro AM, Okamoto OK, Jacobsson L, Cederkrantz E, Washiyama K, Aneheim E, Palm S, Jensen H, Tuma MC, Chammas R, Hultborn R, Albertsson P - PLoS ONE (2015)

Tissue distributions of 211At-MX35 and 211At-Rebmab200.211At-MX35 (filled bars) and 211At-Rebmab200 (open bars). Results are given as mean ± standard deviation of percent injected activity per gram tissue (%-IA/g). *P<0.05 by Student’s t-test. Abbreviation RBM L&R is the red bone marrow taken from left and right femur.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4430291&req=5

pone.0126298.g003: Tissue distributions of 211At-MX35 and 211At-Rebmab200.211At-MX35 (filled bars) and 211At-Rebmab200 (open bars). Results are given as mean ± standard deviation of percent injected activity per gram tissue (%-IA/g). *P<0.05 by Student’s t-test. Abbreviation RBM L&R is the red bone marrow taken from left and right femur.
Mentions: The distribution results were cross-evaluated; the biodistribution of 211At-MX35 was compared with that of 211At-Rebmab200 (Fig 3), and the biodistribution of 125I-MX35 was compared with that of 125I-Rebmab200 (Fig 4). There were no or only minor differences between humanized and murine MX35. A significant difference (P<0.05) was associated with a slightly lower retention in the blood of 211At-Rebmab200-treated mice versus mice treated with 211At-MX35 (Fig 3). There was also higher uptake in the throat (thyroid) of free 125I than 211At (Fig 4), indicating that conjugated astatinated antibodies were more stable than directly iodinated antibodies.

Bottom Line: 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.Taken together, our data support the further development of Rebmab200 for radioimmunotherapy and diagnostics.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Physics, Sahlgrenska Academy, University of Gothenburg,Gothenburg, Sweden.

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.

No MeSH data available.


Related in: MedlinePlus