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


Authors: Dong, Y.; Eskandari, R.; Ray, C.; Granlund, K. L.; Dos Santos-Cunha, L.; Miloushev, V. Z.; Tee, S. S.; Jeong, S.; Aras, O.; Chen, Y. B.; Cheng, E. H.; Hsieh, J. J.; Keshari, K. R.
Article Title: Hyperpolarized MRI visualizes Warburg effects and predicts treatment response to mTOR inhibitors in patient-derived ccRCC xenograft models
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. © 2019 American Association for Cancer Research.
Journal Title: Cancer Research
Volume: 79
Issue: 1
ISSN: 0008-5472
Publisher: American Association for Cancer Research  
Date Published: 2019-01-01
Start Page: 242
End Page: 250
Language: English
DOI: 10.1158/0008-5472.Can-18-2231
PUBMED: 30459151
PROVIDER: scopus
PMCID: PMC6318024
DOI/URL:
Notes: Article -- Export Date: 1 February 2019 -- Source: Scopus
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MSK Authors
  1. Yingbei Chen
    221 Chen
  2. Yiyu Dong
    16 Dong
  3. Emily H Cheng
    55 Cheng
  4. Omer Aras
    29 Aras
  5. Sui Seng   Tee
    7 Tee
  6. Chelsea Elizabeth Ray
    2 Ray
  7. Sangmoo Jeong
    3 Jeong