Fig. 4.

Normalization window as a function of dose and time. Higher doses of antiangiogenic treatment over time increase vessel pruning, which in turn decreases the effective vascular density and impairs vascular efficiency. As a result the fraction of perfused vessels and the region of optimal perfusion decrease. These dose- and time-dependent effects create a normalization window within which drug delivery is optimized. (Inset) Schematic presents the effects of dose and time on the normalization window (adapted from ref. 2).