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Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population

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Abstract

Purpose

Non-invasive imaging is central to hepatocellular carcinoma (HCC) diagnosis; however, conventional modalities are limited by smaller tumors and other chronic diseases that are often present in patients with HCC, such as cirrhosis. This pilot study evaluated the feasibility of (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid ([18F]FSPG) positron emission tomography (PET)/X-ray computed tomography (CT) to image HCC. [18F]FSPG PET/CT was compared to standard-of-care (SOC) magnetic resonance imaging (MRI) and CT, and [11C]acetate PET/CT, commonly used in this setting. We report the largest cohort of HCC patients imaged to date with [18F]FSPG PET/CT and present the first comparison to [11C]acetate PET/CT and SOC imaging. This study represents the first in a US HCC population, which is distinguished by different underlying comorbidities than non-US populations.

Procedures

xC− transporter RNA and protein levels were evaluated in HCC and matched liver samples from The Cancer Genome Atlas (n = 16) and a tissue microarray (n = 83). Eleven HCC patients who underwent prior MRI or CT scans were imaged by [18F]FSPG PET/CT, with seven patients also imaged with [11C]acetate PET/CT.

Results

xC− transporter RNA and protein levels were elevated in HCC samples compared to background liver. Over 50 % of low-grade HCCs and ~70 % of high-grade tumors exceeded background liver protein expression. [18F]FSPG PET/CT demonstrated a detection rate of 75 %. [18F]FSPG PET/CT also identified an HCC devoid of typical MRI enhancement pattern. Patients scanned with [18F]FSPG and [11C]acetate PET/CT exhibited a 90 and 70 % detection rate, respectively. In dually positive tumors, [18F]FSPG accumulation consistently resulted in significantly greater tumor-to-liver background ratios compared with [11C]acetate PET/CT.

Conclusions

[18F]FSPG PET/CT is a promising modality for HCC imaging, and larger studies are warranted to examine [18F]FSPG PET/CT impact on diagnosis and management of HCC. [18F]FSPG PET/CT may also be useful for phenotyping HCC tumor metabolism as part of precision cancer medicine.

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Acknowledgments

This work was supported by National Institutes of Health grant 6P30CA068485, Vanderbilt University institutional support to the Center for Molecular Probes, and a Vanderbilt Trans-Institutional Programs Award. Piramal Imaging provided a portion of the radiochemistry materials used in this study. The authors wish to thank Dr. Michael Schulte for assistance with creating the molecular pathway in Fig. 1.

Author information

Authors and Affiliations

  1. Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Gina Kavanaugh, Jason Williams, Michael L. Nickels & H. Charles Manning

  2. Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Gina Kavanaugh, Jason Williams, Andrew Scott Morris, Michael L. Nickels, Ronald Walker & H. Charles Manning

  3. Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Gina Kavanaugh, Jason Williams, Michael L. Nickels & H. Charles Manning

  4. Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Ronald Walker & H. Charles Manning

  5. Piramal Imaging GmbH, Berlin, Germany

    Norman Koglin & Andrew W. Stephens

  6. Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    M. Kay Washington

  7. Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    Sunil K. Geevarghese

  8. Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    Qi Liu

  9. Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    Qi Liu & Yu Shyr

  10. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    Dan Ayers & Yu Shyr

  11. Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA

    Yu Shyr

  12. Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

  13. Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

  14. Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA

    H. Charles Manning

  15. Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232, USA

    H. Charles Manning

  16. Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, USA

    H. Charles Manning

Authors
  1. Gina Kavanaugh
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  2. Jason Williams
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  3. Andrew Scott Morris
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  4. Michael L. Nickels
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  5. Ronald Walker
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  6. Norman Koglin
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  7. Andrew W. Stephens
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  8. M. Kay Washington
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  9. Sunil K. Geevarghese
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  10. Qi Liu
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  11. Dan Ayers
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  12. Yu Shyr
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  13. H. Charles Manning
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Corresponding author

Correspondence to H. Charles Manning.

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Conflict of Interest

Norman Koglin and Andrew W. Stephens are employees of Piramal Imaging GmbH and are co-inventors of the compound under investigation and/or have ownership interests in Piramal Imaging.

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Kavanaugh, G., Williams, J., Morris, A.S. et al. Utility of [18F]FSPG PET to Image Hepatocellular Carcinoma: First Clinical Evaluation in a US Population. Mol Imaging Biol 18, 924–934 (2016). https://doi.org/10.1007/s11307-016-1007-0

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  • DOI: https://doi.org/10.1007/s11307-016-1007-0

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