Multinuclear NMR and MRI Reveal an Early Metabolic Response to mTOR Inhibition in Sarcoma

Area of Science:

• Oncology
• Biochemistry
• Medical Imaging

Background:

• PI3K and mTOR pathway hyperactivation is common in sarcomas.
• This pathway regulates anaerobic glycolysis, impacting cancer cell energy production.
• Identifying predictive biomarkers for rapalog therapy is crucial for patient selection.

Purpose of the Study:

• To evaluate phenotypic and metabolic effects of PI3K/mTOR pathway inhibition.
• To assess the role of this pathway in regulating glycolysis in human sarcomas.
• To explore hyperpolarized MRI as a monitoring strategy for therapeutic response.

Main Methods:

• Utilized a multimodality approach including in vitro cell line studies and in vivo animal models.
• Administered short- and long-term rapamycin treatment to sarcoma cell lines.
• Employed hyperpolarized Magnetic Resonance Imaging (MRI) to monitor metabolic changes in vivo.

Main Results:

• Observed decreased lactate production and cell growth inhibition in vitro following rapamycin treatment.
• Quantitatively monitored a similar reduction in lactate production in vivo using hyperpolarized MRI.
• Demonstrated that hyperpolarized MRI can differentiate reduced cell proliferation from cell death.

Conclusions:

• Hyperpolarized MRI is a sensitive, noninvasive technique for monitoring PI3K/mTOR pathway drug-induced perturbations in sarcomas.
• This imaging method can assess treatment response by tracking metabolic shifts.
• The findings support the use of hyperpolarized MRI in clinical trials for sarcoma patients.