دورية أكاديمية
Blood pharmacokinetics of various monoclonal antibodies labeled with a new trifunctional chelating reagent for simultaneous conjugation with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid and biotin before radiolabeling.
| العنوان: | Blood pharmacokinetics of various monoclonal antibodies labeled with a new trifunctional chelating reagent for simultaneous conjugation with 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid and biotin before radiolabeling. |
|---|---|
| المؤلفون: | Wang Z; Department of Oncology, Lund University Hospital, Sweden., Mårtensson L, Nilsson R, Bendahl PO, Lindgren L, Ohlsson T, Sjögren HO, Strand SE, Tennvall J |
| المصدر: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2005 Oct 01; Vol. 11 (19 Pt 2), pp. 7171s-7177s. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: The Association Country of Publication: United States NLM ID: 9502500 Publication Model: Print Cited Medium: Print ISSN: 1078-0432 (Print) Linking ISSN: 10780432 NLM ISO Abbreviation: Clin Cancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Denville, NJ : The Association, c1995- |
| مواضيع طبية MeSH: | Antibodies, Monoclonal/*pharmacokinetics , Biotin/*pharmacokinetics , Chelating Agents/*pharmacology , Heterocyclic Compounds, 1-Ring/*pharmacokinetics , Immunoconjugates/*chemistry , Radioimmunotherapy/*methods, Animals ; Antibodies, Monoclonal/blood ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/pharmacology ; Antibodies, Monoclonal, Humanized ; Antibodies, Monoclonal, Murine-Derived ; Avidin/chemistry ; Doxorubicin/chemistry ; Doxorubicin/pharmacology ; Immunoglobulin G/chemistry ; Quality Control ; Radioimmunodetection ; Radioisotopes/chemistry ; Rats ; Rituximab ; Time Factors ; Trastuzumab |
| مستخلص: | Purpose: Knowledge of the blood pharmacokinetics of monoclonal antibodies is crucial in deciding the optimal time for starting the administration of a "clearing agent" or using a "clearing device." The primary purpose was to investigate whether the pharmacokinetics of various antibodies labeled with the same chelator and (111)In differed significantly after i.v. injection in immunocompetent rats. A new trifunctional chelator called "1033" containing a biotin and a radiometal chelation moiety is introduced, making it possible to use only one conjugation procedure for the antibody. Experimental Design: Sixty-five non-tumor-bearing rats were included and divided into four groups (I-IV). The blood pharmacokinetics was investigated for rituximab, BR96, and trastuzumab labeled with 1033 and (111)In (I-III). The whole-body activity and activity uptake in muscle, liver, and kidney, which might explain differences in the early pharmacokinetics in blood, were also measured. hMN14 labeled with another chelator [1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)], but with the same radionuclide ((111)In-biotin-DOTA-hMN14), was studied (IV). The blood pharmacokinetics from another 15 tumor-bearing rats was compared with those of non-tumor-bearing rats (III) by injection of (111)In-1033-BR96. Results: No statistical difference was detected between the groups regarding the blood pharmacokinetics of rituximab, BR96, or trastuzumab. The pharmacokinetics and biodistribution of (111)In-biotin-DOTA-hMN14 exhibited a clear difference compared with others. There were no significant differences in the blood pharmacokinetics of (111)In-1033-BR96 between tumor-bearing rats and non-tumor-bearing rats. Conclusions: Different antibodies labeled with the trifunctional chelator 1033 and (111)In did not exhibit different blood pharmacokinetics, which means that the pharmacokinetics could be predicted irrespective of the IgG1 antibody chosen. A small tumor burden did not change the pharmacokinetics of the radioimmunoconjugates. |
| المشرفين على المادة: | 0 (Antibodies, Monoclonal) 0 (Antibodies, Monoclonal, Humanized) 0 (Antibodies, Monoclonal, Murine-Derived) 0 (BR96-doxorubicin immunoconjugate) 0 (Chelating Agents) 0 (Heterocyclic Compounds, 1-Ring) 0 (Immunoconjugates) 0 (Immunoglobulin G) 0 (Radioisotopes) 1405-69-2 (Avidin) 1HTE449DGZ (1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid) 4F4X42SYQ6 (Rituximab) 6SO6U10H04 (Biotin) 80168379AG (Doxorubicin) P188ANX8CK (Trastuzumab) |
| تواريخ الأحداث: | Date Created: 20051006 Date Completed: 20060223 Latest Revision: 20161124 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1158/1078-0432.CCR-1004-0001 |
| PMID: | 16203818 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1078-0432 |
|---|---|
| DOI: | 10.1158/1078-0432.CCR-1004-0001 |