Bifunctional antibodies

Baxter LT, Yuan F, Jain RK. Pharmacokinetic analysis of the perivascular distribution of bifunctional antibodies and haptens Comparison with experimental data. Cancer Res 1992 52 5838h14. 

Monoclonal antibodies represent a diverse group of therapeutic proteins typically presenting with complex pharmacokinetic properties [10]. For these compounds, more comprehensive, mechanism-based PBPK models have been described [96,97]. Baxter et al. developed and evaluated a bifunctional antibody PBPK model in mice and scaled the model to predict its pharmacokinetics in humans [96]. A membrane-... 

Nolan, O. and O Kennedy, R., Bifunctional antibodies concept, production and apphcations, Biochim. Biophys. Acta, 1040 (1), 1-11, 1990. 

Brennan J, Dillon P, and O Kennedy R (2003) Production, purification and characterisation of genetically derived scFv and bifunctional antibody fragments capable of detecting illicit drug residues. Journal of Chromatography B 786 327-342. 

Nolan O and O Kennedy R (1991) Bifunctional antibodies concepts and applications. International Journal of Clinical and Laboratory Research 22 21-27. 

Bifunctional antibodies that contain antigen-specific binding sites with two different specificities have been produced via genetic engineering as well as chemical techniques [Kufer et al., 2004]. The dual specificity of bispecific antibodies can be used to bring together the molecules or cells that mediate... 

In the bifunctional radiopharmaceuticals, Tc and Re complexes that are suitable for coupling to antibodies are almost square-pyramidal oxo complexes of tetradentate ligands, as mentioned earlier. Spies et al. [65] recently studied the syntheses and structures of rhenium complexes with a tetradentate NS3 tripod ligand 2, 2,, 2"-nitrilotris(ethanethiol) (l in Fig. 9) as an interesting alternative to the oxo complex. Such ligands could lead to weakly polar, trigonal-bipyramidal complexes in which the metal atom is more strongly shielded than in the square-pyramidal oxo complexes. Schemes for the syntheses... 

However, problems are encountered in production of rhenium radionuclides and work is being done to increase the yields of the radionuclides to meet urgent demands for their use in therapy. Moreover, rhenium is not as reactive as technetium. This situation makes rhenium chemistry somewhat specific - optimum conditions in the preparation of rhenium complexes or in antibody labeling using bifunctional ligands must be identified. 

Wong SC, Chan JK, Lo ES, et al. The contribution of bifunctional SkipDewax pretreatment solution, rabbit monoclonal antibodies, and polymer detection systems in immunohistochemistry. Arch. Pathol. Lab. Med. 2007 131 1047-1055. 

Figure 20.18 The bifunctional chelating reagent DTPA may be used to modify amine groups on antibody molecules, forming amide bond linkages. Indium-111 then may be complexed to the chelator group to create a radiolabeled-targeting reagent.

Foglesong, P.D., Winkler, M.A., Price, J.O., Marshall, G.D., Reagh, S.H., Bush, D.A., Hixson, K.S., and West, W.H. (1989) Preparation and analysis of bifunctional immunoconjugates containing monoclonal antibodies OKT3 and BABR1. Cancer Immunol. Immunother. 30(3), 177-184. 

Subramanian, R., and Meares, C.F. (1991) Bifunctional chelating agents for radiometal-labeled monoclonal antibodies. In Cancer Imaging with Radiolabeled Antibodies (D.M. Coldenberg, ed.), pp. 183-199. Kluwer, Boston, MA. 

The purpose of a bifunctional chelator is to link a radiometal covalently to a targeting molecule such as a monoclonal antibody or a receptor-binding peptide. In the case of rhenium, the molecule therefore... 

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