Multimodal Metabolic Imaging of Resistance to Antiandrogens in Prostate Cancer Patient-Derived Xenografts

Motivation: Many advanced prostate cancer (PCa) patients receiving anti-androgens (Enzalutamide) as the first line of treatment, develop resistance which relapses into metastatic castrate-resistant PCa (mCRPC) with an alarming low survival rate of only 28%. Goal(s): The overarching goal of this research is thus to develop personalized metabolic imaging modality to target treatment strategies of different metabolic sub-types of PCa. Approach: By targeting pyruvate-to-lactate metabolism by hyperpolarized [1-13C]-pyruvate MR and fatty acid oxidation by 18F-FPIA PET. Results: HP-MR is effective in classifying resistant and sensitive PCa and interrogating an MCT1 inhibitor, Syrosingopine, that is effective in sensitizing a resistant phenotype. Impact: The research described has the potential to lead practice-changing recommendations by detecting therapeutic efficacy earlier and changing the patient to a different therapeutic regiment. This research also has the potential to recommend combination therapy in the clinic to resistant patients.