ZdTha inhibited tumor growth with prolonged reductions of tumor relative blood volume (rBV), relative blood flow (rBF), and tumor vessel permeability. (A) The rBV change in the ZdTha group remained at a lower level than that of the Zd group (P = 0.0003) until day 6, then it increased at 12 d. (B) A significant reduction in tumor rBF at 2 d was noted in the ZdTha group, but not the other 3 groups (P<0.05 for all 3 groups). (C) The tumor volume transfer constant (Ktrans) change was much lower In the ZdTha group compared to controls at 4 h (P<0.0001), 2 d (P = 0.0026), and 6 d (P = 0.0500). This indicated that combined ZdTha therapy enhanced the transient reduction in tumor vessel permeability. (D) Compared to controls, the ZdTha group maintained low tumor fractional volumes, ve, from 2 d (P = 0.0420) to 12 d (P = 0.0812), except at 6 d. In the Tha group, ve sharply rose at 12 d. This group exhibited a relatively large amount of necrosis, which may cause an increase in extracellular fluid, compared to the other groups. The rectangular shadow indicates the transient window of tumor vessel normalization induced by the combined ZdTha treatment (Tables S3, S4).