Background: Monoclonal antibodies have confirmed their merit as biotherapeutics across a wide spectrum of diseases, including cancer, heart disease, infection, and immune disorders. Materials and Methods: The dynamics of Zr-89-labelled monoclonal antibodies (MAb) after injection into the human body are modelled. This modified biokinetic model can be used for dose assessment not only for Zr-89-labelled MAb tumour visualization but also for diagnostic and radiation therapy with other MAb-labelled radionuclides. The created modified biokinetic model is based on experimental data from the literature. The cumulative Zr-89 activity in organs and tissues per Bq of administered activity is calculated with the WinAct program. Results: For the organs receiving the highest radiation exposure, the average absorbed doses were estimated with IDAC 2.1 software. The results from the modelled calculations are compared with new published experimental diagnostic results from real patients. The calculations reveal that the organs which received the highest dose were the spleen, liver, kidneys, and red bone marrow (doses of 1.54, 1.33, 0.81 and 0.82 mGy/MBq, respectively). In the modified biokinetic model, the organs exhibiting the highest dose were the liver, gallbladder wall, spleen, pancreas, and kidneys (at 1.07, 0.77, 0.70, 54 and 0.44 mGy/MBq, respectively), when the injection was associated with monoclonal antibodies. Conclusion: The developed biokinetic model is in good agreement with direct measurements and can be considered a first step for simulating the radiopharmaceutical dosimetry of the Zr-89 isotope.
机构:
Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Tinianow, Jeff N.
Gill, Herman S.
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Gill, Herman S.
Ogasawara, Annie
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Ogasawara, Annie
Flores, Judith E.
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Flores, Judith E.
Vanderbilt, Alexander N.
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Vanderbilt, Alexander N.
Luis, Elizabeth
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Luis, Elizabeth
Vandlen, Richard
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Vandlen, Richard
Darwish, Martine
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Darwish, Martine
Junutula, Jagath R.
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Junutula, Jagath R.
Williams, Simon-P.
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
Williams, Simon-P.
Marik, Jan
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Genentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USAGenentech Inc, Dept Biomed Imaging, Genentech Res & Early Dev, San Francisco, CA 94080 USA
机构:
Uppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, SwedenUppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden
Garousi, Javad
Anderson, Ken G.
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KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, SwedenUppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden
Anderson, Ken G.
Mitran, Bogdan
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Uppsala Univ, Div Mol Imaging, Dept Med Chem, SE-75183 Uppsala, SwedenUppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden
Mitran, Bogdan
Pichl, Marie-Louise
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Uppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, SwedenUppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden
Pichl, Marie-Louise
Stahl, Stefan
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KTH Royal Inst Technol, Div Prot Technol, SE-10691 Stockholm, SwedenUppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden
Stahl, Stefan
Orlova, Anna
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Uppsala Univ, Div Mol Imaging, Dept Med Chem, SE-75183 Uppsala, SwedenUppsala Univ, Inst Immunol Genet & Pathol, Dag Hammarskjolds Vag 20, SE-75185 Uppsala, Sweden