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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.

Author:
  • Zhongmin Wang
  • Linda Mårtensson
  • Rune Nilsson
  • Pär-Ola Bendahl
  • Lars Lindgren
  • Tomas G Ohlsson
  • Hans Olov Sjögren
  • Sven-Erik Strand
  • Jan Tennvall
Publishing year: 2005
Language: English
Pages: 7171-7177
Publication/Series: Clinical Cancer Research
Volume: 11
Issue: 19 Pt 2
Document type: Journal article
Publisher: American Association for Cancer Research

Abstract english

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.

Keywords

  • Cancer and Oncology

Other

Published
  • ISSN: 1078-0432
Sven-Erik Strand
E-mail: sven-erik [dot] strand [at] med [dot] lu [dot] se

Project manager

Systemic Radiation Therapy Group

32

Professor emeritus

Medical Radiation Physics, Lund

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