Fig 1.
Representative Ktrans maps for HS766t, Mia PaCa-2 and Su.86.86 tumor type from DCE-MRI (L-R).
As demonstrated in the histogram, Ktrans 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.
Fig 2.
Time-course imaging result of DCE-MRI and DW-MRI.
A) Time-courses of normalized mean Ktrans values. The mean values of normalized Ktrans 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, P>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.
Fig 3.
ADC maps and histograms of DW-MRI from representative animals at different time points pre- and post-treatment initiation.
A dramatically increased ADCs observed in HS766T, but not in the other two tumor types.
Fig 4.
(A) Histological staining of γ-H2AX, a marker for DNA damage response mechanisms, in PDAC tumors pre- and 48hr post-TH-302 treatment (50 mg/kg). Expression of γ -H2AX was increased in TH-302 treated Hs766t and Mia PaCa-2 tumors when compared to saline control. No detectable change in γ-H2AX staining was observed between Su.86.86 treated and saline tumors. (B) Pimonidazole staining as biomarker of physical tumor hypoxia. Pimonidazole Hydrochloride was injected 2hr prior to tumor removal. The extent of hypoxia was greatest in Hs766t tumors and least in SU.86.86 with Mia PaCa-2 tumors moderately hypoxic. These images are representative images of each tumor type. Scale bars = 200 μM.