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
Journal
European Journal of Nuclear Medicine and Molecular Imaging
Journal Volume
46
Journal Issue
4
Pages
810-820
Date Issued
2019
Author(s)
Huang Y.-Y.
Ho B.-Y.
Shiue C.-Y.
Kuo H.-C.
Abstract
Purpose: (4S)-4-(3- 18 F-Fluoropropyl)-l-glutamate (FSPG) positron emission tomography (PET) reflects system x C ? 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 18 F-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. ? 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
SDGs
Other Subjects
4 (3 fluoropropyl)glutamate f 18; fluorodeoxyglucose f 18; tracer; unclassified drug; 4-(3-fluoropropyl)glutamic acid; fluorodeoxyglucose f 18; glutamic acid derivative; adult; animal experiment; animal model; Article; cancer diagnosis; cancer patient; cancer tissue; clinical article; comparative study; contrast enhancement; controlled clinical trial; controlled study; diagnostic accuracy; distant metastasis; exploratory research; female; follow up; histopathology; human; human cell; human tissue; liver metastasis; male; maximum standardized uptake value; middle aged; mouse; nonhuman; open study; pancreas adenocarcinoma; pancreas tissue; positron emission tomography-computed tomography; proof of concept; radiodiagnosis; sensitivity and specificity; standardized uptake value; standardized uptake value ratio; tissue specificity; x-ray computed tomography; adenocarcinoma; adverse event; clinical trial; diagnostic imaging; metastasis; pancreas tumor; pathology; positron emission tomography-computed tomography; procedures; prospective study; safety; tumor cell line; Adenocarcinoma; Cell Line, Tumor; Female; Fluorodeoxyglucose F18; Glutamates; Humans; Male; Middle Aged; Neoplasm Metastasis; Pancreatic Neoplasms; Positron Emission Tomography Computed Tomography; Prospective Studies; Safety
Publisher
Springer Berlin Heidelberg
Type
journal article