Hyperpolarized 13C MRI as a New Tool to Detect Early Treatment Response and Metabolic Heterogeneity in Advanced Renal Cell Carcinoma

Motivation: Hyperpolarized (HP) 13C-pyruvate metabolic MRI may provide a solution to the pressing unmet need to discriminate early therapeutic response vs resistance in advanced renal cell carcinoma (RCC). Goal(s): To evaluate, for the first time, whether pyruvate-to-lactate conversion (kPL) is an early and sensitive response marker to systemic RCC therapies. Approach: Three patients with advanced RCC underwent HP MRI at baseline and again 3-4-week after treatment initiation (N=2). Results: HP 13C MRI detected a 50-100% kPL decrease at 4-weeks, prior to definitive clinical radiographic response (~3 months). Inter- and intratumoral metabolic heterogeneity may inform on subsequent therapeutic efficacy. Impact: Management of advanced/metastatic RCC in the salvage setting is challenging and options are limited. Our initial positive findings highlight how HP 13C MRI's unique sensitivity to early treatment response/resistance may be leveraged to improve outcomes and avoid toxic, ineffective therapies.