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Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI

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Abstract

Purpose

We optimized acido-chemical exchange saturation transfer (acidoCEST) magnetic resonance imaging (MRI), a method that measures extracellular pH (pHe), and translated this method to the radiology clinic to evaluate tumor acidosis.

Procedures

A CEST-FISP MRI protocol was used to image a flank SKOV3 tumor model. Bloch fitting modified to include the direct estimation of pH was developed to generate parametric maps of tumor pHe in the SKOV3 tumor model, a patient with high-grade invasive ductal carcinoma, and a patient with metastatic ovarian cancer. The acidoCEST MRI results of the patient with metastatic ovarian cancer were compared with DCE MRI and histopathology.

Results

The pHe maps of a flank model showed pHe measurements between 6.4 and 7.4, which matched with the expected tumor pHe range from past acidoCEST MRI studies in flank tumors. In the patient with metastatic ovarian cancer, the average pHe value of three adjacent tumors was 6.58, and the most reliable pHe measurements were obtained from the right posterior tumor, which favorably compared with DCE MRI and histopathological results. The average pHe of the kidney showed an average pHe of 6.73 units. The patient with high-grade invasive ductal carcinoma failed to accumulate sufficient agent to generate pHe measurements.

Conclusions

Optimized acidoCEST MRI generated pHe measurements in a flank tumor model and could be translated to the clinic to assess a patient with metastatic ovarian cancer.

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References

  1. Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    Article  CAS  PubMed  Google Scholar 

  2. Chen LQ, Pagel MD (2015) Evaluating pH in the extracellular tumor microenvironment using CEST MRI and other imaging methods. Adv Radiol. doi:10.1155/2015/206405

    PubMed  PubMed Central  Google Scholar 

  3. Gatenby RA, Gawlinski ET, Gmitro AF et al (2006) Acid mediated tumor invasion: a multidisciplinary study. Cancer Res 66:5216–5223

    Article  CAS  PubMed  Google Scholar 

  4. Estrella V, Chen T, Lloyd M (2013) Acidity generated by the tumor microenvironment drives local invasion. Cancer Res 73:1524–1535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Akhenblit PA, Pagel MD (2016) Recent advances in targeting tumor energy metabolism with tumor acidosis as a biomarker of drug efficacy. J Cancer Sci Therapy 8:20–29

    Article  Google Scholar 

  6. Chen LQ, Howison CM, Jeffery JJ (2013) Evaluations of extracellular pH within in vivo tumors using acidoCEST MRI. Magn Reson Med 72:1408–1417

    Article  PubMed  PubMed Central  Google Scholar 

  7. Sheth VR, Li Y, Chen LQ (2012) Measuring in vivo tumor pHe with CEST-FISP MRI. Magn Reson Med 67:760–768

    Article  PubMed  Google Scholar 

  8. Liu G, Li Y, Sheth VR, Pagel MD (2012) Imaging in vivo extracellular pH with a single PARACEST MRI contrast agent. Mol Imaging 1:47–57

    Google Scholar 

  9. Sheth VR, Liu G, Li Y, Pagel MD (2012) Improved pH measurements with a single PARACEST MRI contrast agent. Contrast Media Mol Imaging 1:26–34

    Article  Google Scholar 

  10. Aime S, Calabi L, Biondi L (2005) Iopamidol: exploring the potential use of a well-established x ray contrast agent for MRI. Magn Reson Med 53:830–834

    Article  CAS  PubMed  Google Scholar 

  11. Liepinsh E, Otting G (1996) Proton exchange rates from amino acid side chains—implications for image contrast. Magn Reson Med 1:30–42

    Article  Google Scholar 

  12. Jones KM, Randtke ER, Howison CM et al (2015) Measuring extracellular pH in a lung fibrosis model with acidoCEST MRI. Mol Imaging and Biol 2:177–184

    Article  Google Scholar 

  13. Woessner DE, Zhang S, Merritt MEG, Sherry AD (2005) Numerical solution of the Bloch equations provides insights into the optimum design of PARACEST agents for MRI. Magn Reson Med 53:790–799

    Article  CAS  PubMed  Google Scholar 

  14. Moon BF, Jones KM, Chen LQ et al (2015) A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH. Contrast Media Mol Imaging 10:446–455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hingorani DV, Montano LA, Randtke EA et al (2015) A single diamagnetic catalyCEST MRI contrast agent that detects cathepsin B enzyme activity by using a ratio of two CEST signals. Contrast Media Mol Imaging 11:130–138

    Article  PubMed  PubMed Central  Google Scholar 

  16. Dopfert J, Zaiss M, Witte C, Schroeder L (2014) Ultrafast CEST imaging. J Magn Reson 243:47–53

    Article  PubMed  Google Scholar 

  17. Muller-Lutz A, Khalil N, Schmitt B et al (2014) Pilot study of iopamidol-based quantitative pH imaging on a clinical 3 T MR scanner. Magn Reson Mater Phy 27:477–485

  18. Harston GWJ, Tee YK, Blockley N et al (2015) Identifying the ischaemic penumbra using pH-weighted magnetic resonance imaging.  Brain A J Neurol 138:36-42

  19. Ma B, Blakeley JO, Hong X et al (2016) Applying amide proton transfer-weighted MRI to distinguish pseudoprogression from true progression in malignant gliomas. J Magn Reson Imaging. doi:10.1002/jmri.2515

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Authors and Affiliations

  1. Biomedical Engineering Graduate Interdisciplinary Program, University of Arizona, Tucson, AZ, USA

    Kyle M. Jones, Phillip H. Kuo & Mark D. Pagel

  2. Department of Medical Imaging, University of Arizona, 1515 N. Campbell Ave., Tucson, AZ, 85724-5024, USA

    Edward A. Randtke, Christine M. Howison, Phillip H. Kuo & Mark D. Pagel

  3. University of Arizona Cancer Center, Tucson, AZ, USA

    Eriko S. Yoshimaru, Setsuko K. Chambers, Phillip H. Kuo & Mark D. Pagel

  4. Division of Hematology-Oncology, University of Arizona, Tucson, AZ, USA

    Pavani Chalasani

  5. Department of Pathology, University of Arizona, Tucson, AZ, USA

    Robert R. Klein

  6. Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ, USA

    Setsuko K. Chambers

Authors
  1. Kyle M. Jones
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  2. Edward A. Randtke
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  3. Eriko S. Yoshimaru
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  4. Christine M. Howison
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  5. Pavani Chalasani
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  6. Robert R. Klein
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  7. Setsuko K. Chambers
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  8. Phillip H. Kuo
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  9. Mark D. Pagel
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Corresponding author

Correspondence to Mark D. Pagel.

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The authors declare that they have no conflict of interest.

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Jones, K.M., Randtke, E.A., Yoshimaru, E.S. et al. Clinical Translation of Tumor Acidosis Measurements with AcidoCEST MRI. Mol Imaging Biol 19, 617–625 (2017). https://doi.org/10.1007/s11307-016-1029-7

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  • DOI: https://doi.org/10.1007/s11307-016-1029-7

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