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Abstract #2421

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

1Radiology and Biomedical Imaging, UCSF, San Francisco, CA, USA; 2Neurological Surgery, UCSF, San Francisco, CA, USA

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.