Synthesis and Evaluation of Amine Reactive Carboranyl Derivatives for Application to Boron-10 Containing Polymers
The use of monoclonal antibodies to selectively deliver boron-10 to cancer cells for boron neutron capture therapy (BNCT) has been under active investigation for over 20 years (1). A major difficulty in the application of boronated antibodies is the high concentrations of boron-10 required in the tumor tissue (e.g. 35 mg B-10/g tissue) (2). Simple calculations have shown that each antibody molecule must have a minimum of 600–1000 boron atoms to achieve the concentrations of boron-10 required (1-4). Seemingly, the only way to achieve such a large number of boron atoms per antibody molecule is to incorporate the boron into a polymer, then attach the boronated polymer to the antibody. Further, the coupling of boron containing polymer with the antibody must be accomplished in a manner that does not adversely affect its antigen binding or dramatically change the physical properties of the antibody (e.g. net ionic charge). Thus, it seems that a reasonable objective would be to prepare a neutral boronated polymer which could be site-specifically attached to the antibody.
KeywordsAcetonitrile Boron Carboxylate Adduct MeOH
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- 1.Alam, F., Barth, R.F. & Soloway, A.H. (1989) Boron Containing Immunoconjugates for Neutron Capture Therapy of Cancer and for Immunocytochemistry. Antibody, Immunoconj. Radiopharm. 2, 145–163.Google Scholar
- 5.Middaugh, R.L. (1975) Closo-Boron Hydrides, in Boron Hydride Chemistry, ed. Muetterties, E.L. (Academic Press, New York) Chapt. 8, pp 273–300,.Google Scholar
- 6.Grimes, R.N. (1970) Carboranes (Academic Press, New York).Google Scholar
- 11.Wilbur, D.S., Hamlin, D.K., Laramore, G.E. & Griffin, T.W. (1993) Preparation of meta-Carborane Derivatives by Thermal Rearrangement in a Small Scale Laboratory Apparatus. Proceedings of 5th Int. Symposium on Neutron Capture Therapy (this volume).Google Scholar
- 12.Wilbur, D.S., Hamlin, D.K., Livesey, J.C., Srivastava, R.R., Laramore, G.E. & Griffin T.W. (1993) Preparation of meta-Carboranylpropyl-2-nitroimidazole Derivatives for Application to BNCT. Proceedings of 5th Int. Symposium on Neutron Capture Therapy (this volume).Google Scholar