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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

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

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.

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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).

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Authors and Affiliations

  1. Department of Nuclear Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    Mei-Fang Cheng, Ya-Yao Huang, Chyng-Yann Shiue & Rouh-Fang Yen

  2. Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, 7 Chung-Shan South Rd., Taipei, 10002, Taiwan, Republic of China

    Bing-Ying Ho, Ting-Chun Kuo, Hsun-Chuan Kuo & Yu-Wen Tien

  3. Department of Anesthesiology, Wang Fang Hospital, Taipei Medical University, Taipei, Taiwan

    Bing-Ying Ho

  4. School of Pharmacy, National Taiwan University, Taipei, Taiwan

    Ling-Wei Hsin

  5. Molecular Imaging Center, National Taiwan University, Taipei, Taiwan

    Ling-Wei Hsin & Chyng-Yann Shiue

  6. Center for Innovative Therapeutics Discovery, National Taiwan University, Taipei, Taiwan

    Ling-Wei Hsin

  7. Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

    Yung-Ming Jeng

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  1. Mei-Fang Cheng
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Correspondence to Yu-Wen Tien.

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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.

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Cheng, MF., Huang, YY., Ho, BY. et al. 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. Eur J Nucl Med Mol Imaging 46, 810–820 (2019). https://doi.org/10.1007/s00259-018-4251-5

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