Figure 2

Gd concentration within blood and glioma tissue over time following intravenous Gd-dendrimer infusions at doses of 0.03 mmol Gd/kg bw and 0.09 mmol Gd/kg bw. A) Blood concentrations of Gd-dendrimers measured in the superior sagittal sinus following 0.03 mmol Gd/kg bw infusion. Gd-G1 (n=6), Gd-G2 (n=5), Gd-G3 (n=5), and lowly conjugated Gd-G4 (n=5) dendirmers imaged for 1 hour. Standard Gd-G4 (n=6), Gd-G5 (n=6), Gd-G6 (n=5), Gd-G7 (n=6), and Gd-G8 (n=5) dendrimers imaged for 2 hours. Error bars represent standard deviations. B) Blood concentrations of Gd-dendrimers measured in the superior sagittal sinus following 0.09 mmol Gd/kg bw infusion. Gd-G1 (n=4), Gd-G2 (n=6), Gd-G3 (n=6), lowly conjugated Gd-G4 (n=4), standard Gd-G4 (n=6), Gd-G5 (n=6), Gd-G6 (n=5), Gd-G7 (n=5), and Gd-G8 (n=6). Blood concentrations of Gd-G6, Gd-G7, and Gd-G8 dendrimers not shown for clarity. C) At both doses, lowly conjugated Gd-G4 dendrimers (molecular weight 24.4 kD) remain for a short period of time within the extravascular tumor space. 0.03 mmol Gd/kg bw dose n=5, 0.09 mmol Gd/kg bw dose n=4. D) At both doses, standard Gd-G4 dendrimers (molecular weight 39.8 kD) remain for longer within the extravascular tumor space. 0.03 mmol Gd/kg bw dose n=6, 0.09 mmol Gd/kg bw dose n=6. E) At both doses, Gd-G5 dendrimers accumulate within the extravascular tumor space. 0.03 mmol Gd/kg bw dose n=6, 0.09 mmol Gd/kg bw dose n=6. F) At the 0.03 mmol Gd/kg bw dose (n=5), Gd-G6 dendrimers do not extravasate out of tumor microvasculature. At the 0.09 mmol Gd/kg bw dose (n=5), Gd-G6 dendrimers extravasate. G) At the 0.03 mmol Gd/kg bw dose (n=6), Gd-G7 dendrimers do not extravasate. At the 0.09 mmol Gd/kg bw dose (n=5), Gd-G7 dendrimers extravasate. H) Irrespective of dose, Gd-G8 dendrimers do not extravasate out of brain tumor microvasculature. 0.03 mmol Gd/kg bw dose n=5, 0.09 mmol Gd/kg bw dose n=6. In panels C through H, Gd tumor concentrations and standard deviations shown are weighted for total tumor volume.