A Clearance Step will become Increasingly Crucial for Pretargeted Tumor Therapy when Tumor Accumulation is Improved

This is a commentary on a paper we published in Cancer Biother Radiopharm 2010. This commentary addresses related concerns about adding a separate clearing agent in the pretargeted tumor therapy. Previous investigations of tumor pretargeting mostly focused on utilizing the characteristic rapid clearance of a small therapeutic effector to limit toxicity exposure to normal tissues, but at a price of reduced tumor accumulation. Nevertheless, at least in theory, this reduction of tumor accumulation is not inevitable. The effector structure should be able to be modulated for its highest tumor accumulation while keeping the normal tissue background of the free effector negligible. However, so far little effort has been made in this area. In connection with the reduction of the toxicity to normal tissues, inclusion of a clearing step is well known. This commentary is to indicate that, in the pretargeted tumor therapy, inclusion of a clearance step will be more crucial when tumor accumulation of the effector is improved. It is the prerequisite to redeem the benefit of improved tumor accumulation.