Scheme of the pharmacokinetic model (A) and experimental data (B-D) that describe the αvβ3-targeting kinetics of cRGD-SPPM in tumor-bearing mice. (A) Angiogenic endothelium compartment (black box) is proposed to model the accumulation rate (ka) of cRGD-SPPM. The tumor extravascular compartment (blue box) and blood compartment (red box) can be subtracted from cRAD-SPPM control, yielding only the angiogenic endothelium compartment for analysis of cRGD-SPPM nanoprobes. (B-D) cRGD-SPPM targeting kinetic curves in A549, MDA-MB-231 and U87 tumors, respectively. When fitted to a one-compartment pharmacokinetic model, cRGD-SPPM showed accumulation rates (ka) of 0.24 (R2=0.51), 0.22 (R2=0.87) and 0.24 (R2=0.83) min-1 in A549, MDA-MB-231 and U87 tumors, respectively. The slopes of the linear fit (red lines) from data points after 10 mins also indicate a continuous but slower accumulation of the cRGD-SPPM, with slopes of 0.19 (R2=0.88), 0.18 (R2=0.57) and 0.20 (R2=0.90) min-1 for A549, MDA-MB-231 and U87 tumors, respectively.