FIG. 8.

EPR tumor oxygen imaging after pyruvate injection and effect of pyruvate injection on treatment outcome. (A) EPR oxygen imaging of subcutaneous Hs766t, MiaPaCa-2, and SU.86.86 tumors pre- and post (10–60 min) i.v. pyruvate administration. Representative T₂-weighted anatomical MRI and pO₂ maps are provided in N = 4 biological replicates per tumor type. (B) Temporal changes of percentage hypoxic fraction (<10 mmHg) of pyruvate-treated pancreatic ductal adenocarcinoma tumors. Data are presented as mean ± SD. Proposed histological predictive biomarkers for pyruvate sensitivity. (C) Local tumor control (%) of Hs766t, MiaPaCa-2, and SU.86.86 tumors treated with saline, TH-302 alone (80mg/kg·5 days I.P.), or TH-302 following a 30 min pretreatment with exogenous pyruvate (1.15mmol/kg pyruvate i.v. 30 min before 80mg/kg TH-302 I.P.·5 days). Response was measured as percentage of surviving animals as mice are removed from study when tumors reach 2000 mm³. Pyruvate pretreatment significantly improved local control of Hs766t (p < 0.00225) and MiaPaCa-2 tumors with no measurable effect against SU.86.86. (D) Mean survival (days) of mice with pancreatic tumors treated with TH-302 and TH-302 in combination with pyruvate pretreatment. N = 10 mice per treatment group. A two-tailed Student's t-test was used to determine significance. **p < 0.01. Adapted from Ref. (65) with permission. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars