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Minerva Biotecnologica 2009 March;21(1):5-19

Copyright © 2009 EDIZIONI MINERVA MEDICA

lingua: Inglese

Molecular endoradiotherapy of cancer

Haberkorn U. ^1-2, Eisenhut M. ³, Altmann A. ^1-2, Mier W. ¹

¹ Department of Nuclear Medicine, University of Heidelberg Heidelberg, Germany 2 Clinical Cooperation Unit Nuclear Medicine DKFZ and University of Heidelberg Heidelberg, 69120, Germany 3 Department of Radiopharmaceutical Chemistry, DKFZ Heidelberg, Germany

For the successful treatment of cancer new imaging and treatment modalities based on the biological properties of malignant tissues are needed. Specific targeting has been mainly achieved using antibodies and recently also with peptides. When labeled with b-emitting radioisotopes these agents are suitable for endoradiotherapy and exploit the targeting potential of high affinity binders for highly specific therapeutic applications which has been realized for antibodies against CD20 or peptides binding to somatostatin receptors such as 90Y-DOTATOC. These radiopharmaceuticals offer the potential to develop patient specific therapies and might provide the means to go beyond the possibilities of current chemotherapy and radiation therapy. A major advantage lies in the ability to identify patients profiting from endoradiotherapy by labeling the binder with an isotope suitable for PET or SPECT measurements and then use the same molecule for treatment after labeling with a therapeutic isotope. These achievements encourage more research towards the identification of new specifically binding molecules. The development of new biomolecules relies on the identification of lead compounds and on the screening of various derivatives of these compounds one at a time. The principle of high-troughput methods for the identification of novel high affinity binders is to generate a vast library of possible variants of the molecule of interest and screen the population for the few variants that show the property of interest. The attracting feature of the concept arises from 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.