Prospective comparison of (4S)-4-(3- 18 F-fluoropropyl)-L-glutamate versus 18 F-fluorodeoxyglucose PET/CT for detecting metastases from pancreatic ductal adenocarcinoma: a proof-of-concept study

Eur J Nucl Med Mol Imaging. 2019 Apr;46(4):810-820. doi: 10.1007/s00259-018-4251-5. Epub 2019 Jan 11.

Abstract

Purpose: (4S)-4-(3-18F-Fluoropropyl)-L-glutamate (FSPG) positron emission tomography (PET) reflects system xC- transporter (xCT) expression. FSPG PET has been used to detect brain, lung, breast and liver cancer with only modest success. There is no report on the use of FSPG PET in pancreatic ductal adenocarcinoma (PDAC), presumably because of normal xCT expression in the pancreas. Nonetheless, the tissue-specific expression of xCT in the pancreas suggests that FSPG PET may be ideal for identifying metastasized PDAC.

Methods: The performance of FSPG in detecting PDAC metastases was compared with that of 18F-fluorodeoxyglucose (FDG) in small-animal PET studies in seven PDAC tumour-bearing mice and in prospective PET/computed tomography (CT) studies in 23 patients with tissue-confirmed PDAC of stage III or stage IV. All PET/CT results were correlated with the results of histopathology or contrast-enhanced CT (ceCT) performed 3 and 6 months later.

Results: In the rodent model, FSPG PET consistently found more PDAC metastases earlier than FDG PET. FSPG PET showed a trend for a higher sensitivity, specificity and diagnostic accuracy than FDG PET in detecting PDAC metastases in a patient-based analysis: 95.0%, 100.0% and 95.7%, and 90.0%, 66.7% and 90.0%, respectively. In a lesion-based analysis, FSPG PET identified significantly more PDAC metastases, especially in the liver, than FDG PET (109 vs. 95; P = 0.0001, 95% CI 4.9-14.6). The tumour-to-background ratios for FSPG and FDG uptake on positive scans were similar (FSPG 4.2 ± 4.3, FDG 3.6 ± 3.0; P = 0.44, 95% CI -1.11 to 0.48), despite a lower tumour maximum standardized uptake value in FSPG-avid lesions (FSPG 4.2 + 2.3, FDG 7.7 + 5.7; P = 0.002, 95% CI 0.70-4.10). Because of the lower physiological activity of FSPG in the liver, FSPG PET images of the liver are more easy to interpret than FDG PET images, and therefore the use of FSPG improves the detection of liver metastasis.

Conclusion: FSPG PET is superior to FDG PET in detecting metastasized PDAC, especially in the liver.

Keywords: FSPG; Liver metastases; Pancreatic cancer; Positron emission tomography; xC transporter system.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adenocarcinoma / diagnostic imaging*
  • Adenocarcinoma / pathology*
  • Cell Line, Tumor
  • Female
  • Fluorodeoxyglucose F18*
  • Glutamates*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Pancreatic Neoplasms / diagnostic imaging*
  • Pancreatic Neoplasms / pathology*
  • Positron Emission Tomography Computed Tomography / adverse effects
  • Positron Emission Tomography Computed Tomography / methods*
  • Prospective Studies
  • Safety

Substances

  • 4-(3-fluoropropyl)glutamic acid
  • Glutamates
  • Fluorodeoxyglucose F18