Endoradiotherapy with Peptides - Status and Future Development

Uwe      Haberkorn; Michael      Eisenhut; Annette      Altmann; Walter      Mier

doi:10.2174/092986708783497256

Abstract

With the advances in molecular biology and biochemistry new imaging and treatment modalities based on the biological properties of tissues have been developed where important progress has been achieved using antibodies and peptides. This paper will concentrate on peptide vectors. When labeled with therapeutic radioisotopes these agents are suitable for endoradiotherapy and exploit the targeting potential for highly specific treatment which has been realized for antibodies against CD20 or peptides binding to somatostatin receptors. This novel class of pharmaceuticals offers the potential to develop specific therapies beyond the possibilities of current chemotherapy and radiation therapy. Furthermore, these achievements can be seen as proof of principle and encourage more research towards the identification of new specifically binding molecules. Activities towards the development of new biomolecules can be based on biotechnology methods. Rational design uses informations obtained from structure-activity relationship studies and conformational analyses of peptide structures. This approach relies on the identification of lead compounds and screening of various derivatives of these compounds. In contrast to rational design the central idea of black box approaches is to create vast libraries of possible variants of molecules and screen the population for the few compounds that show the property of interest. The attracting feature relies on the huge number of candidate molecules that can be used for further evaluation. After the characterization of the structure-function relationships for the lead compounds found in this process further improvement by rational design of analogs can be performed.

Keywords: Endoradiotherapy, peptides, phage display, ribosome display, targeted therapy

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