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

Mol Imaging Biol. 2016 Dec;18(6):924-934. doi: 10.1007/s11307-016-1007-0.


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.

Keywords: Cancer imaging; FSPG; HCC; PET.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / chemistry
  • Adult
  • Aged
  • Amino Acid Transport System y+ / genetics
  • Amino Acid Transport System y+ / metabolism
  • Carbon Radioisotopes
  • Carcinoma, Hepatocellular / diagnostic imaging*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Glutamates / chemistry*
  • Glutamic Acid / chemistry*
  • Humans
  • Liver Neoplasms / diagnostic imaging*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals / chemistry
  • Sequence Analysis, RNA
  • Tissue Array Analysis


  • 4-(3-fluoropropyl)glutamic acid
  • Acetates
  • Amino Acid Transport System y+
  • Carbon Radioisotopes
  • Glutamates
  • Radiopharmaceuticals
  • SLC7A11 protein, human
  • Glutamic Acid