Hyperpolarized MRI visualizes Warburg effects and predicts treatment response to mTOR inhibitors in patient-derived CCRCC xenograft models

Yiyu Dong, Roozbeh Eskandari, Chelsea Ray, Kristin L. Granlund, Lidia Dos Santos-Cunha, Vesselin Z. Miloushev, Sui Seng Tee, Sangmoo Jeong, Omer Aras, Ying Bei Chen, Emily H. Cheng, James J. Hsieh, Kayvan R. Keshari

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

The ever-changing tumor microenvironment constantly challenges individual cancer cells to balance supply and demand, presenting tumor vulnerabilities and therapeutic opportunities. Everolimus and temsirolimus are inhibitors of mTOR (mTORi) approved for treating metastatic renal cell carcinoma (mRCC). However, treatment outcome varies greatly among patients. Accordingly, administration of mTORi in mRCC is diminishing, which could potentially result in missing timely delivery of effective treatment for select patients. Here, we implemented a clinically applicable, integrated platform encompassing a single dose of [1-13C] pyruvate to visualize the in vivo effect of mTORi on the conversion of pyruvate to lactate using hyperpolarized MRI. A striking difference that predicts treatment benefit was demonstrated using two preclinical models derived from patients with clear cell RCC (ccRCC) who exhibited primary resistance to VEGFRi and quickly succumbed to their diseases within 6 months after the diagnosis of metastasis without receiving mTORi. Our findings suggest that hyperpolarized MRI could be further developed to personalize kidney cancer treatment. Significance: These findings demonstrate hyperpolarized [1-13C]pyruvate MRI as a tool for accurately assessing the clinical success of mTOR inhibition in patients with ccRCC.

Original languageEnglish (US)
Pages (from-to)242-250
Number of pages9
JournalCancer research
Volume79
Issue number1
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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