Figure 1.

Schematic representation of the route of the antibody/antibody fragment after administration. After intravenous administration the injected antibodies/antibody fragments (A) enter the blood stream and circulate throughout the whole body. Both the size and binding properties of the molecule used influences tumor targeting in various ways. (B) It is necessary that antibodies/antibody fragments effectively extravasate into the tumor interstitium. In general, the enhanced permeability and retention (EPR) effect favors tumor accumulation of larger molecules. (C) In the tumor interstitium, molecules travel through tumor extracellular matrix (ECM) to reach tumor cells. Smaller molecules diffuse faster in the more densely packed ECM. (D) For tumor retention, the antibodies/antibody fragments should have sufficient affinity for their target molecule on the surface of the tumor cells. (E) Binding site barrier: molecules with high affinities have restricted penetration inside the tumor mass, which is more apparent for larger molecules. (F) Upon binding, antibodies are endocytosed and degraded in lysosomes. Cellular catabolism reduces the local concentration, which is the driving force of diffusive transport. Systemic clearance (via liver and/or kidneys) reduces the overall concentration of the administered molecules, thereby affecting intratumoral distribution.