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Hyperpolarized MRI Visualizes Warburg Effects and Predicts Treatment Response to mTOR Inhibitors in Patient-Derived

Yiyu Dong1, Roozbeh Eskandari2,3, Chelsea Ray1

  • 1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.

Cancer Research
|November 22, 2018
PubMed

Insights

Hyperpolarized MRI using [1-13C] pyruvate can assess mTOR inhibitor effectiveness in metastatic renal cell carcinoma. This approach helps personalize treatment by predicting patient response to therapy.

Area of Science:

  • Oncology
  • Medical Imaging
  • Biochemistry

Background:

  • Metastatic renal cell carcinoma (mRCC) treatment outcomes vary with mTOR inhibitors (mTORi).
  • Decreasing mTORi use in mRCC may lead to missed therapeutic opportunities for some patients.
  • Understanding treatment response is crucial for personalized oncology.

Purpose of the Study:

  • To develop a hyperpolarized MRI method to visualize the in vivo metabolic effects of mTOR inhibitors.
  • To assess the potential of [1-13C] pyruvate MRI for predicting treatment benefit in clear cell RCC (ccRCC).

Main Methods:

  • Implementation of a clinically applicable platform using a single dose of [1-13C] pyruvate.
  • Utilizing hyperpolarized Magnetic Resonance Imaging (MRI) to monitor pyruvate-to-lactate conversion.
  • Testing the method in preclinical models of ccRCC with primary resistance to VEGFR inhibitors.

Main Results:

  • Demonstrated a striking difference in metabolic response to mTORi that predicts treatment benefit.
  • Successfully visualized the in vivo effect of mTORi on pyruvate metabolism.
  • Identified hyperpolarized MRI as a tool to assess mTOR inhibition efficacy.

Conclusions:

  • Hyperpolarized [1-13C] pyruvate MRI can accurately assess clinical success of mTOR inhibition in ccRCC.
  • This imaging technique offers potential for personalizing kidney cancer treatment strategies.
  • Further development of hyperpolarized MRI could improve patient selection for mTORi therapy.

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