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Nonuniform dose distributions among disseminated tumor cells can be a significant limiting factor in targeted α therapy. This study examines how cocktails of radiolabeled antibodies can be formulated to overcome this limitation.Cultured MDA-MB-231 human breast cancer cells were treated with different concentrations of a cocktail of 4 fluorochrome-conjugated monoclonal antibodies. The amount of each antibody bound to each cell was quantified using flow cytometry. A spreadsheet was developed to "arm" the antibodies with any desired radionuclide and specific activity, calculate the absorbed dose to each cell, and perform a Monte Carlo simulation of the surviving fraction of cells after exposure to cocktails of different antibody combinations. Simulations were performed for the α-particle emitters (211)At, (213)Bi, and (225)Ac.Activity delivered to the least labeled cell can be increased by 200

作者:Jordan B, Pasternack;Jason D, Domogauer;Alisha, Khullar;John M, Akudugu;Roger W, Howell

来源:Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2014 年 55卷 12期

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作者:
Jordan B, Pasternack;Jason D, Domogauer;Alisha, Khullar;John M, Akudugu;Roger W, Howell
来源:
Journal of nuclear medicine : official publication, Society of Nuclear Medicine 2014 年 55卷 12期
标签:
Monte Carlo alpha particle antibody cocktails disseminated tumor cells flow cytometry isolated tumor cells radioimmunotherapy radionuclide specific activity targeted alpha therapy
Nonuniform dose distributions among disseminated tumor cells can be a significant limiting factor in targeted α therapy. This study examines how cocktails of radiolabeled antibodies can be formulated to overcome this limitation.Cultured MDA-MB-231 human breast cancer cells were treated with different concentrations of a cocktail of 4 fluorochrome-conjugated monoclonal antibodies. The amount of each antibody bound to each cell was quantified using flow cytometry. A spreadsheet was developed to "arm" the antibodies with any desired radionuclide and specific activity, calculate the absorbed dose to each cell, and perform a Monte Carlo simulation of the surviving fraction of cells after exposure to cocktails of different antibody combinations. Simulations were performed for the α-particle emitters (211)At, (213)Bi, and (225)Ac.Activity delivered to the least labeled cell can be increased by 200