| Radioimmunotherapy with anti-CD66 antibody: improving the biodistribution using a physiologically based pharmacokinetic model. | |
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MedLine Citation:
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PMID: 20150257 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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To improve radioimmunotherapy with anti-CD66 antibody, a physiologically based pharmacokinetic (PBPK) model was developed that was capable of describing the biodistribution and extrapolating between different doses of anti-CD66 antibody. METHODS: The biodistribution of the (111)In-labeled anti-CD66 antibody of 8 patients with acute leukemia was measured. The data were fitted to 2 PBPK models. Model A incorporated effective values for antibody binding, and model B explicitly described mono- and bivalent binding. The best model was selected using the corrected Akaike information criterion. The predictive power of the model was validated comparing simulations and (90)Y-anti-CD66 serum measurements. The amount of antibody (range, 0.1-4 mg) leading to the most favorable therapeutic distribution was determined using simulations. RESULTS: Model B was better supported by the data. The fits of the selected model were good (adjusted R(2) > 0.91), and the estimated parameters were in a physiologically reasonable range. The median deviation of the predicted and measured (90)Y-anti-CD66 serum concentration values and the residence times were 24% (range, 17%-31%) and 9% (range, 1%-64%), respectively. The validated model predicted considerably different biodistributions for dosimetry and therapeutic settings. The smallest (0.1 mg) simulated amount of antibody resulted in the most favorable therapeutic biodistribution. CONCLUSION: The developed model is capable of adequately describing the anti-CD66 antibody biodistribution and accurately predicting the time-activity serum curve of (90)Y-anti-CD66 antibody and the therapeutic serum residence time. Simulations indicate that an improvement of radioimmunotherapy with anti-CD66 antibody is achievable by reducing the amount of administered antibody; for example, the residence time of the red marrow could be increased by a factor of 1.9 +/- 0.3 using 0.27 mg of anti-CD66 antibody. |
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Authors:
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Peter Kletting; Thomas Kull; Donald Bunjes; Bettina Mahren; Markus Luster; Sven N Reske; Gerhard Glatting |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-11 |
Journal Detail:
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Title: Journal of nuclear medicine : official publication, Society of Nuclear Medicine Volume: 51 ISSN: 1535-5667 ISO Abbreviation: J. Nucl. Med. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-03 Completed Date: 2010-04-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217410 Medline TA: J Nucl Med Country: United States |
Other Details:
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Languages: eng Pagination: 484-91 Citation Subset: IM |
Affiliation:
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Klinik f?r Nuklearmedizin, Universit?t Ulm, Ulm, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Antibodies / administration & dosage, immunology*, metabolism, therapeutic use* Antigens, CD / immunology* Cell Adhesion Molecules / immunology* Female Humans Leukemia / metabolism, physiopathology, radiotherapy Male Middle Aged Models, Biological* Radioimmunotherapy* Reproducibility of Results Tissue Distribution Yttrium Radioisotopes / chemistry |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; 0/Antigens, CD; 0/CD66 antigens; 0/Cell Adhesion Molecules; 0/Yttrium Radioisotopes |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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