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



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.



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.



[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.
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Gina
G
Kavanaugh
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Jason
J
Williams
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Andrew Scott
AS
Morris
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Michael L
ML
Nickels
Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Ronald
R
Walker
Piramal Imaging GmbH, Berlin, Germany.
Norman
N
Koglin
Piramal Imaging GmbH, Berlin, Germany.
Andrew W
AW
Stephens
Department of Pathology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
M Kay
MK
Washington
Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Sunil K
SK
Geevarghese
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.|Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Qi
Q
Liu
Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Dan
D
Ayers
Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.|Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.|Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
Yu
Y
Shyr
Vanderbilt University Institute of Imaging Science, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Vanderbilt Center for Molecular Probes, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.|Department of Chemistry, Vanderbilt University, Nashville, TN, 37232, USA. henry.c.manning@vanderbilt.edu.
H Charles
HC
Manning
D000085:Acetates / Q000737:chemistry; D000328:Adult; D000368:Aged; D027182:Amino Acid Transport System y+ / Q000235:genetics / Q000378:metabolism; D002250:Carbon Radioisotopes; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D005260:Female; D005971:Glutamates / Q000737:chemistry*; D018698:Glutamic Acid / Q000737:chemistry*; D006801:Humans; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000737:chemistry; D017423:Sequence Analysis, RNA; D046888:Tissue Array Analysis
C000623325:4-(3-fluoropropyl)glutamic acid; D000085:Acetates; D027182:Amino Acid Transport System y+; D002250:Carbon Radioisotopes; D005971:Glutamates; D019275:Radiopharmaceuticals; C118895:SLC7A11 protein, human; D018698:Glutamic Acid
Cancer imaging; FSPG; HCC; PET
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