In vivo detection of distal tumor glycolytic flux stimulated by hepatic ablation in a breast cancer model using hyperpolarized 13C MRI

Hepatic thermal ablation therapy can result in c-Met-mediated off-target stimulation of distal tumor growth. The purpose of this study was to determine if a similar effect on tumor metabolism could be detected in vivo with hyperpolarized 13C MRI. In this prospective study, female Fisher rats (n = 28, 120–150 g) were implanted with R3230 rat breast adenocarcinoma cells and assigned to either: sham surgery, hepatic radiofrequency ablation (RFA), or hepatic RFA + adjuvant c-Met inhibition with PHA-665752 (RFA + PHA). PHA-665752 was administered at 0.83 mg/kg at 24 h post-RFA. Tumor growth was measured daily. MRI was performed 24 h before and 72 h after treatment on 14 rats, and the conversion of 13C-pyruvate into 13C-lactate within each tumor was quantified as lactate:pyruvate ratio (LPR). Comparisons of tumor growth and LPR were performed using paired and unpaired t-tests. Hepatic RFA alone resulted in increased growth of the distant tumor compared to sham treatment (0.50 ± 0.13 mm/day versus 0.11 ± 0.07 mm/day; p