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.
(2005) In Clinical Cancer Research 11(19 Pt 2). p.7171-7177- Abstract
- 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 In-111 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... (More)
- 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 In-111 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 In-111 (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 In-111-1033-BR96. Results: No statistical difference was detected between the groups regarding the blood pharmacokinetics of rituximab, BR96, or trastuzumab. The pharmacokinetics and biodistribution of In-111-biotin-DOTA-hMN14 exhibited a clear difference compared with others. There were no significant differences in the blood pharmacokinetics of In-111-1033-BR96 between tumor-bearing rats and non-tumor-bearing rats. Conclusions: Different antibodies labeled with the trifunctional chelator 1033 and In-111 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/144849
- author
- Wang, Zhongmin LU ; Mårtensson, Linda LU ; Nilsson, Rune LU ; Bendahl, Pär-Ola LU ; Lindgren, Lars ; Ohlsson, Tomas G LU ; Sjögren, Hans Olov LU ; Strand, Sven-Erik LU and Tennvall, Jan LU
- organization
- publishing date
- 2005
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Clinical Cancer Research
- volume
- 11
- issue
- 19 Pt 2
- pages
- 7171 - 7177
- publisher
- American Association for Cancer Research
- external identifiers
-
- pmid:16203818
- wos:000232238400019
- scopus:26444545539
- ISSN
- 1078-0432
- DOI
- 10.1158/1078-0432.CCR-1004-1001
- language
- English
- LU publication?
- yes
- id
- 94af8ec0-02e5-4ae6-b31b-b3bd4192c47f (old id 144849)
- alternative location
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16203818&dopt=Abstract
- http://clincancerres.aacrjournals.org/content/11/19/7171s.long
- date added to LUP
- 2016-04-01 11:56:33
- date last changed
- 2022-01-26 20:32:46
@article{94af8ec0-02e5-4ae6-b31b-b3bd4192c47f,
abstract = {{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 In-111 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 In-111 (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 In-111-1033-BR96. Results: No statistical difference was detected between the groups regarding the blood pharmacokinetics of rituximab, BR96, or trastuzumab. The pharmacokinetics and biodistribution of In-111-biotin-DOTA-hMN14 exhibited a clear difference compared with others. There were no significant differences in the blood pharmacokinetics of In-111-1033-BR96 between tumor-bearing rats and non-tumor-bearing rats. Conclusions: Different antibodies labeled with the trifunctional chelator 1033 and In-111 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.}},
author = {{Wang, Zhongmin and Mårtensson, Linda and Nilsson, Rune and Bendahl, Pär-Ola and Lindgren, Lars and Ohlsson, Tomas G and Sjögren, Hans Olov and Strand, Sven-Erik and Tennvall, Jan}},
issn = {{1078-0432}},
language = {{eng}},
number = {{19 Pt 2}},
pages = {{7171--7177}},
publisher = {{American Association for Cancer Research}},
series = {{Clinical Cancer Research}},
title = {{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.}},
url = {{http://dx.doi.org/10.1158/1078-0432.CCR-1004-1001}},
doi = {{10.1158/1078-0432.CCR-1004-1001}},
volume = {{11}},
year = {{2005}},
}