ABSTRACT
Cancer cells have a higher proliferation rate than normal cells. In consequence, their demand for various nutrients and vitamins is signicantly increased. Efcient uptake of these vital factors is often met by up-regulation of their specic receptors. Several vitamins have therefore been explored as carrier molecules for drug delivery to cancer cells. Most prominently, derivatives of the vitamin folic acid have been widely used as radiotracers for diagnosis or as vehicles to deliver cytotoxicity (Müller 2012, Vlahov and Leamon 2012). Together with folic acid, B12 is essential as a cofactor for various steps in central metabolism, and cancer cells have an increased requirement of both vitamins. However, compared to folic acid, the use of B12 derivatives for tumor targeting is more challenging for several reasons: (1) Chemically, B12 is the most complex vitamin. (2) In the human body, B12 has a very complicated transport and uptake system, consisting of three transport proteins and several membranebound receptors. This constrains the design of tumor-targeting drugs, because they need to retain binding afnity to the transport proteins. (3) Even rapidly dividing
15.1 Introduction .................................................................................................. 241 15.2 Vitamin B12 and Its Transport Proteins ........................................................242
