In Vivo Detection of PI3K Pathway Inhibition by Hyperpolarized 13C MRSI at 14 Tesla

Myriam Marianne Chaumeil¹, Subramanian Sukumar¹, Humsa Venkatesh¹, Christopher Ward¹, Kristen R. Scott¹, Tomoko Ozawa², C David James², John Kurhanewicz¹, Daniel B. Vigneron¹, Sarah J. Nelson¹, Sabrina M. Ronen¹

In vivo inhibition of the PI3K pathway by Everolimus was evaluated using hyperpolarized (HP) ¹³C MRSI in subcutaneous tumors in mice at 14 Tesla. Whereas lactate-to-pyruvate ratio was increased in control animals, this ratio was decreased by 78% and 35% in treated animals relative to controls after 2 and 7 days, respectively. The drop in lactate-to-pyruvate ratio following Everolimus treatment is in line with the findings in treated cells and likely indicates a decrease in LDH activity in treated tumors. This preliminary in vivo study demonstrates the likely value of HP ¹³C studies of pyruvate for noninvasive monitoring PI3K inhibition.