کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485261 | 1114350 | 2012 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Dose Dependence of Intratumoral Perivascular Distribution of Monoclonal Antibodies
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کلمات کلیدی
carcinoembryonic antigen - آنتی ژن carcinoembryonicMacromolecular drug delivery - تحویل داروی مقوی مولکولیProtein delivery - تحویل پروتئینMicrodistribution - توزیع میکروDrug transport - حمل مواد مخدرCancer - سرطانPreclinical pharmacokinetics - فارماکوکینتیک پیشکلامیMathematical models - مدل ریاضیTransport barriers - موانع حمل و نقلTumor penetration - نفوذ تومور
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Intravenously delivered antibodies have been previously found to distribute in a perivascular fashion in a variety of tumor types and despite targeting a range of different antigens. Properties of both the antibody and the targeted antigen, such as the administered dose, binding affinity, and antigen metabolic half-life, are predicted to influence the observed perivascular distribution. Here, the effect of antibody dose on the perivascular distribution is determined using an unbiased image analysis approach to quantify the microscopic distribution of the antibody around thousands of blood vessels per tumor. This method allows the quantitative determination of the localization of blood vessels, extravasated antibody, and tumor antigen following the administration of antibody doses covering two orders of magnitude in the dose range commonly utilized in preclinical studies. A mathematical model of antibody extravasation, diffusion, binding, and endocytosis in a Krogh cylinder geometry with parameters directly measured or taken from the literature is quantitatively consistent with the experimentally determined profiles. A previously reported scaling analysis is employed to extend these results to any tumor model in which the antigen density and turnover rate are known, allowing facile quantitative prediction of the minimum antibody dose required for complete tumor saturation. © 2011 Wiley Periodicals, Inc. and the American Pharmacists Association.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 2, February 2012, Pages 860-867
Journal: Journal of Pharmaceutical Sciences - Volume 101, Issue 2, February 2012, Pages 860-867
نویسندگان
John J. Rhoden, Karl Dane Wittrup,