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
1Radiology, UCSF, San Francisco, CA,
United States; 2Brain tumor Research Center, UCSF, San Francisco,
CA, United States
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.