ΔR2* calculated from normal tissue in a single mouse acquired on three different days.

<p>In this case, first- and second- pass circulation of CA injection is observed. Only first –pass circulation was used in DSC analysis.</p

Summary of the K^trans reproducibility measurements.

<p>Summary of the K^trans reproducibility measurements.</p

VIFs from Gd-DTPA (a) and P792 (c).

<p>VIFs were smoothed by temporal spline-fit function for Gd-DTPA (b) and P792 (d).</p

Summary of the rBV reproducibility measurements. Arbitrary units (AU).

<p>Summary of the rBV reproducibility measurements. Arbitrary units (AU).</p

K^trans parametric maps of a single mouse acquired on three different days (Day 1, Day 3 and Day 5) within one week (a); Histogram of K^trans in tumor ROI for all 3 days (b); Difference of histograms (c).

<p>Cumulative histograms of K^trans in tumor ROI on three different imaging days (d).</p

Signal amplitude change of DSC on tumor tissue (left column) and normal tissue (right column).

<p>Three rows represent three separate measurements (top row: Day 1; middle row: Day 3; bottom row: Day 5) for a single animal. The 95% confidence limits for significant changes in signal are shown on each graph (dot line), The bolus was injected at 0 seconds.</p

Time-course imaging result of DCE-MRI and DW-MRI.

<p>A) Time-courses of normalized mean K^trans values. The mean values of normalized K^trans decreased 69% for TH-302 treated mice in Hs766t tumors, decreased 46% for Mia PaCa-2 tumors and increased 5% in SU.86.86 tumors. B) Changes in normalized mean tumor ADC values over time. A substantial increase in relative mean ADCs was observed for the TH-302 treated group at post- 24 and 48 hours (29% increasing for 24h, p<0.01; 17% increasing for 48h, p<0.01). MIA PaCa-2 is not statistically significant different between conducted groups (8% increasing for 24h, <i>P</i>>0.05; 4% increasing for 48h, p>0.05). For SU.86.86, no significant change was detected by DW-MRI for both TH-302 and control group (3% decreasing for 24h, p>0.05; 0.5% increasing for 48h, p>0.05). The normalization was calculated by the average of the difference of pre- and post-treatment in Th302 group relative to average of the difference of pre- and post-treatment in control group. Error bars stand for standard deviation.</p

ADC maps and histograms of DW-MRI from representative animals at different time points pre- and post-treatment initiation.

<p>A dramatically increased ADCs observed in HS766T, but not in the other two tumor types.</p

Representative K^trans maps for HS766t, Mia PaCa-2 and Su.86.86 tumor type from DCE-MRI (L-R).

<p>As demonstrated in the histogram, K^trans generated from HS766t and Mia-PaCa-2 tumors were dramatically decreased 48 hours after TH-302 treatment compared to pre-treatment values. There were no significant changes observed for a SU.86.86 mouse at the same time point.</p

pH electrode results indicate that MIA PaCa-2 tumors exhibit “steal” Effect in response to hydralazine.

<p>Mice bearing subcutaneous SU.86.86 (n = 7), Hs766t (n = 3) or MIA PaCa-2 (n = 4) flank tumors were anesthetized and tumor pH measurements were obtained. A reference electrode was inserted under the skin of the mouse in a non-tumor site while the pH electrode was inserted up to 1.3 cm into the center of each tumor. Two measurements were taken at each time point and averaged. Following initial pH measurements, mice were administered 10 mg/kg hydralazine via ip injection. Tumor pH was measured for 3 hours following treatment. Data reported represents the average maximum change in each cohort, the average pH change for each cohort and the single animal maximum pH change for each cohort. Data is reported as mean change in pH ± SEM. * <i>P</i><0.05; **<i>P</i><0.007.</p