Figure 4
Modeled pharmacokinetic parameters of lower generation Gd-dendrimers. A) The increase in Gd-dendrimer generation and size from that of Gd-G1 to that of lowly conjugated Gd-G4 results in a decrease in particle transvascular flow rate (Ktrans). Large tumors have higher Ktrans values. B) Lowly conjugated Gd-G4 dendrimer distribution within the glioma extravascular extracellular space (ve) is influenced to the greatest extent by the decrease in Ktrans. Large tumors have higher ve values. C) Fractional plasma volume (vp) within glioma vasculature is maintained across dendrimer generations. Large tumors have higher vp values. Large circles (Gd-G1 n= 4, Gd-G2 n=6, Gd-G3 n=7, and Gd-G4 n=2) represent large tumors (> 50 mm3), small circles (Gd-G1 n=4, Gd-G2 n=6, Gd-G3 n=5, and Gd-G4 n=6) represent small tumors (< 50 mm3), horizontal bars represent mean of observations weighted with respect to individual tumor volumes. Shown are Bonferroni corrected p-values from the nine post hoc comparisons for the three parameters, NS = not significant. D) There a more widespread distribution of Gd-G1 particles within the extravascular extracellular tumor space as shown by the greater range of ve values; whereas, there is a more focal distribution of lowly conjugated Gd-G4 dendrimers as shown by the lower range of ve values. Shown are voxels surviving censorship. Tumor volumes, in mm3, for tumors shown are 104 (Gd-G1) and 162 (lowly conjugated Gd-G4).