Hyperpolarized 13C MRS Detection of Reduced Pyruvate-Lactate Conversion Following PI3K Inhibition

Christopher S. Ward¹, Humsa Venkatesh¹, Alissa Brandes¹, Mark van Criekinge¹, Hagit Dafni¹, John Kurhanewicz¹, C. David James², Daphne A. Haas-Kogan², Sabrina M. Ronen¹

This study demonstrates the efficacy of hyperpolarized ¹³C MRS as a method to detect target modulation following PI3K inhibitor treatment in MDA-MB-231 breast adenocarcinoma and glioma neurosphere cells. ¹³C MR spectra revealed that treatment with 50 M LY294002 for 40 hr reduced conversion of hyperpolarized pyruvate to lactate to 7016% of control in MDA-MB-231 and 4514% in GBM. LDH activity assay and Western blotting confirmed this effect to be the result of reduced lactate dehydrogenase levels following PI3K inhibition. This work suggests promising applications for hyperpolarized ¹³C MR as a noninvasive method to monitor responses to targeted anticancer treatments.