Molecular Imaging and Biology

, Volume 18, Issue 6, pp 924–934

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

  • Gina Kavanaugh
  • Jason Williams
  • Andrew Scott Morris
  • Michael L. Nickels
  • Ronald Walker
  • Norman Koglin
  • Andrew W. Stephens
  • M. Kay Washington
  • Sunil K. Geevarghese
  • Qi Liu
  • Dan Ayers
  • Yu Shyr
  • H. Charles Manning
Research Article

DOI: 10.1007/s11307-016-1007-0

Cite this article as:
Kavanaugh, G., Williams, J., Morris, A.S. et al. Mol Imaging Biol (2016) 18: 924. doi:10.1007/s11307-016-1007-0

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.

Key Words

PETFSPGHCCCancer imaging

Copyright information

© World Molecular Imaging Society 2016

Authors and Affiliations

  • Gina Kavanaugh
    • 1
    • 2
    • 3
  • Jason Williams
    • 1
    • 2
    • 3
  • Andrew Scott Morris
    • 2
  • Michael L. Nickels
    • 1
    • 2
    • 3
  • Ronald Walker
    • 2
    • 4
  • Norman Koglin
    • 5
  • Andrew W. Stephens
    • 5
  • M. Kay Washington
    • 6
  • Sunil K. Geevarghese
    • 7
  • Qi Liu
    • 8
    • 9
  • Dan Ayers
    • 10
  • Yu Shyr
    • 9
    • 10
    • 11
  • H. Charles Manning
    • 1
    • 2
    • 3
    • 4
    • 12
    • 13
    • 14
    • 15
    • 16
  1. 1.Vanderbilt University Institute of Imaging ScienceVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of Radiology and Radiological SciencesVanderbilt University Medical CenterNashvilleUSA
  3. 3.Vanderbilt Center for Molecular ProbesVanderbilt University Medical CenterNashvilleUSA
  4. 4.Vanderbilt-Ingram Cancer CenterVanderbilt University Medical CenterNashvilleUSA
  5. 5.Piramal Imaging GmbHBerlinGermany
  6. 6.Department of PathologyVanderbilt University Medical CenterNashvilleUSA
  7. 7.Department of SurgeryVanderbilt University Medical CenterNashvilleUSA
  8. 8.Department of Biomedical InformaticsVanderbilt University School of MedicineNashvilleUSA
  9. 9.Center for Quantitative SciencesVanderbilt University School of MedicineNashvilleUSA
  10. 10.Department of BiostatisticsVanderbilt University School of MedicineNashvilleUSA
  11. 11.Department of Cancer BiologyVanderbilt University School of MedicineNashvilleUSA
  12. 12.Program in Chemical and Physical BiologyVanderbilt University Medical CenterNashvilleUSA
  13. 13.Department of NeurosurgeryVanderbilt University Medical CenterNashvilleUSA
  14. 14.Vanderbilt Institute of Chemical BiologyVanderbilt University Medical CenterNashvilleUSA
  15. 15.Department of Biomedical EngineeringVanderbilt UniversityNashvilleUSA
  16. 16.Department of ChemistryVanderbilt UniversityNashvilleUSA