XIAOMENG ZHANG1, Dutta Prasanta1, Gary Martinez1, N V. Rajeshkumar2, A Le2, A Maitra2, C V. Dang2, Robert J. Gillies1
1cancer imaging, Moffitt cancer center, TAMPA, FL - Florida, United States; 2School of Medicine, Johns Hopkins University,, Baltimore, MD, United States
Development of novel targeted anti-cancer therapies is highly dependent on qualified in-vivo biomarkers for the therapeutic response. Small molecule drug FX11 that inhibits the lactate dehydrogenase A (LDHA) alters cellular energy metabolism, and reduces the tumor progression1. This procedure could be captured in-vivo by monitoring the metabolic conversion rate of 13C-labled substrates using dynamic nuclear polarization (DNP)2. This measurement could be compared with the most common imaging response biomarker: diffusion-weighted MRI (DW-MRI), which is a measure of tumor cellularity. The apparent diffusion coefficient (ADC) of tumors calculated from DW-MRI has been shown to be valuable for predicting early response to therapies in a variety of cancers3. The purpose of this study is to demonstrate the dynamics of metabolic conversion from 13C pyruvate to 13C lactate with FX11 treatment and compare the ability of two response biomarkers: hyperpolarized (HP) 13C-labled magnetic resonance spectroscopy (MRS) and DW-MRI in the drug sensitive tumor Panc253.
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