**11.1 Pre-targeting**

The pretargeting procedure was developed from the concept that the targeting antibody should be separated from the targeting radionuclide through the use of a bispecific antibody (Chang et al., 2002). An alternative approach to improve tumor:blood ratio for RIS is the use of pre-targeting strategies. The pre-targeting strategies have led to significant improvements in T/B ratio and better diagnostic imaging (Dearling & pedley, 2007). Also, pretargeting has been applied successfully for radioimmunoimaging, because the pretargeted antibody is nontoxic. High doses can be administered to saturate antigenic sites at the tumor. Pretargeting strategies for RIT have been applied to achieve higher intratumor concentration of isotope than achieved by conventional RIT (Kraeber–Bodere et al., 2009). The simplest form of pre-targeting is to use a second antibody reagent to clear blood background activity, hence improving the signal:noise ratio and the quality of the image. Immune complexes formed by a second antibody are rapidly removed from the circulation by the reticuloendothelial system, particularly in the liver. In the alternative approach, the administration of antibody and radiolabel are separated. Antibody is allowed to localize to the tumor and sufficient time is allowed for antibody clearance from the blood and non-target tissues (Dearling & pedley, 2007). Radioisotope is then injected separately in a form which can be readily captured by the tumor bound antibody. The approaches using streptavidin/biotin binding systems raised much interest, because the affinity of streptavidin for biotin is exceptionally high (Gruaz-Guyon et al., 2005). In this strategy, the high affinity of the avidin:biotin system is used to capture radiolabeled small molecules from the blood as a two-step imaging method. Antibody-avidin conjugate is injected and allowed to be localized to the tumor and cleared from the blood (Dearling & pedley, 2007). Radioactive avidin is then injected which localizes the tumor by taking advantage of the high affinity and specificity of avidin for biotin (Roland et al., 2010, Dearling & pedley, 2007).
