Purpose To assess in a mouse model whether early or late components of glucose metabolism, exemplified by fluorine 18 (F) fluorodeoxyglucose (FDG) positron emission tomography (PET) and hyperpolarized carbon 13 (C)-pyruvate magnetic resonance (MR) spectroscopy, can serve as indicators of response in ovarian cancer to multityrosine kinase inhibitor pazopanib. Materials and Methods In this Animal Care and Use Committee approved study, 17 days after the injection of 2 × 10 human ovarian SKOV3 tumors cells into 14 female nude mice, treatment with vehicle or pazopanib (2.5 mg per mouse peroral every other day) was initiated. Longitudinal T2-weighted MR imaging, dynamic MR spectroscopy of hyperpolarized pyruvate, and F-FDG PET/computed tomographic (CT) imaging were performed before treatment, 2 days after treatment, and 2 weeks after treatment. Results Pazopanib inhibited ovarian tumor growth compared with control (0.054 g ± 0.041 vs 0.223 g ± 0.112, respectively; six mice were treated with pazopanib and seven were control mice; P < .05). Significantly higher pyruvate-to-lactate conversion (lactate/pyruvate + lactate ratio) was found 2 days after treatment with pazopanib than before treatment (0.46 ± 0.07 vs 0.31 ± 0.14, respectively; P < .05; six tumors after treatment, seven tumors before treatment). This was not observed with the control group or with F-FDG PET/CT imaging. Conclusion The findings suggest that hyperpolarized C-pyruvate MR spectroscopy may serve as an early indicator of response to tyrosine kinase (angiogenesis) inhibitors such as pazopanib in ovarian cancer even when F-FDG PET/CT does not indicate a response. RSNA, 2017 Online supplemental material is available for this article.