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

  • Mei-Fang Cheng
  • Ya-Yao Huang
  • Bing-Ying Ho
  • Ting-Chun Kuo
  • Ling-Wei Hsin
  • Chyng-Yann Shiue
  • Hsun-Chuan Kuo
  • Yung-Ming Jeng
  • Rouh-Fang Yen
  • Yu-Wen TienEmail author
Original Article

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

Pancreatic cancer Liver metastases Positron emission tomography FSPG xC transporter system 

Notes

Acknowledgments

We appreciate the contributions of Ms. Yu-Ning Chang and Dr. Hannes Hagu for their technical support in radiotracer synthesis, and Ms. Pin-Tsen Shih, Ms. Kwanyu Lin and Mr. Chien-Chu Liu for clinical PET/CT scans. We thank the physicians who referred their patients for inclusion in this clinical trial and who reported their follow-up data.

Funding

This study was funded by National Taiwan University Hospital (MOHW104-TD-B-111-04) and the Ministry of Science and Technology (MOST 103–2321-B-002-074, MOST 104–2321-B-002-075, and MOST 104–2314-B-002-134).

Compliance with ethical standards

Conflicts of interest

None.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

259_2018_4251_MOESM1_ESM.pdf (672 kb)
ESM 1 (PDF 672 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Mei-Fang Cheng
    • 1
  • Ya-Yao Huang
    • 1
  • Bing-Ying Ho
    • 2
    • 3
  • Ting-Chun Kuo
    • 2
  • Ling-Wei Hsin
    • 4
    • 5
    • 6
  • Chyng-Yann Shiue
    • 1
    • 5
  • Hsun-Chuan Kuo
    • 2
  • Yung-Ming Jeng
    • 7
  • Rouh-Fang Yen
    • 1
  • Yu-Wen Tien
    • 2
    Email author
  1. 1.Department of Nuclear MedicineNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan
  2. 2.Department of SurgeryNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiRepublic of China
  3. 3.Department of Anesthesiology, Wang Fang HospitalTaipei Medical UniversityTaipeiTaiwan
  4. 4.School of PharmacyNational Taiwan UniversityTaipeiTaiwan
  5. 5.Molecular Imaging CenterNational Taiwan UniversityTaipeiTaiwan
  6. 6.Center for Innovative Therapeutics DiscoveryNational Taiwan UniversityTaipeiTaiwan
  7. 7.Department of PathologyNational Taiwan University Hospital and National Taiwan University College of MedicineTaipeiTaiwan

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