Comparative study of 18F-FAPI-04 and 18F-FDG PET/CT in the initial staging and postoperative metastasis detection of gastric cancer

doi:10.4251/wjgo.120559

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World Journal of Gastrointestinal Oncology

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1948-5204

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastrointest Oncol. Sep 15, 2026; 18(9): 120559
Published online Sep 15, 2026. doi: 10.4251/wjgo.120559

Comparative study of ¹⁸F-FAPI-04 and ¹⁸F-FDG PET/CT in the initial staging and postoperative metastasis detection of gastric cancer

Xiu-Qing Xue, Qing-Bo Li, Hai-Tian Fu, Lu Hou, Ran Wang, Xun Shi, Chun-Jing Yu

Xiu-Qing Xue, Ran Wang, Xun Shi, Department of Nuclear Medicine, The First People’s Hospital of Yancheng, Yancheng 224006, Jiangsu Province, China

Xiu-Qing Xue, Ran Wang, Xun Shi, Department of Nuclear Medicine, The Yancheng Clinical College of Xuzhou Medical University, Yancheng 224006, Jiangsu Province, China

Qing-Bo Li, Hai-Tian Fu, Lu Hou, Chun-Jing Yu, Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, Wuxi 214000, Jiangsu Province, China

Co-first authors: Xiu-Qing Xue and Qing-Bo Li.

Author contributions: Xue XQ and Li QB conceived the idea for the manuscript, acquired and analyzed experimental data, and drafted and revised the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; Fu HT and Hou L acquired experimental data; Wang R and Shi X analyzed experimental data; Yu CJ wrote the manuscript; Fu HT, Hou L, Wang R, Shi X, and Yu CJ contributed to the study design and manuscript revision; and all authors have read and approved the final version of the manuscript.

AI contribution statement: The core contents of this document, including point-to-point replies to reviewers’ comments, academic explanations and revision statements, are all written independently by the authors. Only a small number of sentences were preliminarily drafted and expressions adjusted with AI assistance. AI tools were merely used for partial translation and language polishing to improve English writing fluency. All contents revised with AI assistance have been fully reviewed and verified sentence by sentence by the authors to ensure academic accuracy and rigorous logical thinking.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Affiliated Hospital of Jiangnan University, approval No. LSX2022043.

Clinical trial registration statement: This clinical trial was registered at ClinicalTrials.gov (registration No. NCT05691894; URL: https://clinicaltrials.gov/study/NCT05691894).

Informed consent statement: All patients/participants (or their legal guardians) provided written informed consent prior to their participation in this study. The consent covered the use of their data and samples for research purposes and publication.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.

Data sharing statement: No additional data are available.

Corresponding author: Chun-Jing Yu, DM, Chief Physician, Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, No. 1000 Hefeng Road, Wuxi 214000, Jiangsu Province, China. ycjwxd1978@jiangnan.edu.cn

Received: March 2, 2026
Revised: May 12, 2026
Accepted: June 24, 2026
Published online: September 15, 2026
Processing time: 177 Days and 6.3 Hours

Abstract

BACKGROUND

Accurate clinical staging is fundamental to the precision management of gastric cancer (GC). Nonetheless, the clinical performance of ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) in GC is limited by relatively low sensitivity, particularly for lymph node metastasis (LNM) and peritoneal metastasis (PM).

AIM

To compare ¹⁸F-fibroblast activation protein inhibitor (FAPI)-04 PET/CT with ¹⁸F-FDG PET/CT in patients with newly diagnosed GC and in those with suspected recurrence or metastasis after curative surgery.

METHODS

Twenty-one patients were prospectively enrolled, including 11 with newly diagnosed GC and 10 with suspected postoperative recurrence or metastasis. Each patient underwent both ¹⁸F-FAPI-04 and ¹⁸F-FDG PET/CT within 7 days. Lesions were verified by pathology and/or imaging follow-up. Diagnostic performance and quantitative parameters were compared, including maximum standardized uptake value (SUVmax), tumor-to-background ratio (TBR), FDG-derived metabolic tumor volume (MTV) and total lesion glycolysis (TLG), and FAPI-derived FAPI-avid tumor volume (FTV), and total lesion fibroblast activation protein expression (TLF). The peritoneal cancer index (PCI) was assessed for diffuse peritoneal disease.

RESULTS

Among the 21 patients (237 lesions in total), 11 (52.4%, 11/21) had newly diagnosed GC, and 10 (47.6%, 10/21) had suspected local recurrence or metastasis after surgery; only 1 patient (4.8%, 1/21) had suspected local recurrence. For primary tumors, ¹⁸F-FAPI-04 demonstrated higher uptake and contrast than ¹⁸F-FDG (SUVmax: 11.6 vs 6.5, P = 0.036; TBR: 11.5 vs 5.1, P = 0.009) and yielded higher tracer-specific total-lesion burden metrics (TLF vs TLG: 260.5 vs 57.9, P = 0.036). For LNMs, quantitative uptake and derived parameters were comparable between tracers (SUVmax: 6.6 vs 6.5, P = 0.703; TBR: 5.4 vs 6.4, P = 0.65; FTV vs MTV: 3.1 vs 1.9, P = 0.321; TLF vs TLG: 8.3 vs 6.3, P = 0.654). For PM, ¹⁸F-FAPI-04 showed substantially higher uptake and volumetric burden in nodular disease (SUVmax: 7.1 vs 3.2, P = 0.002; TBR: 7.4 vs 2.4, P = 0.002; FTV vs MTV: 13.2 vs 1.2, P = 0.003; TLF vs TLG: 39.3 vs 3.3, P = 0.004). In diffuse PM, ¹⁸F-FAPI-04 yielded a higher PCI score and higher SUVmax than ¹⁸F-FDG (PCI: 14 vs 2.5, P = 0.012; SUVmax: 8.0 vs 4.7, P = 0.001). For bone metastases, ¹⁸F-FAPI-04 also demonstrated higher uptake and contrast (SUVmax: 11.1 vs 5.5, P < 0.001; TBR: 10.4 vs 5.6, P < 0.001) and differed in tracer-specific total-lesion metrics (TLF vs TLG: 7.7 vs 9.5, P = 0.045). Among the 11 patients with primary GC, the sensitivity of ¹⁸F-FAPI-04 PET/CT for primary tumor detection was 100% compared with 90.9% for ¹⁸F-FDG PET/CT. For detection of LNM and PM, sensitivities were 100% and 100% with ¹⁸F-FAPI-04, vs 75% and 50% with ¹⁸F-FDG, respectively.

CONCLUSION

In this pilot study, we observed trends of higher tracer uptake and lesion-to-background contrast with ¹⁸F-FAPI-04 PET/CT compared to ¹⁸F-FDG PET/CT in primary GC, PMs, and bone metastases. Additionally, ¹⁸F-FAPI-04 PET/CT showed trends of a greater number of metastatic lesions overall, with higher detection yields particularly for PM, suggesting its potential value for initial staging and postoperative assessment in GC.

Keywords: ¹⁸F-fibroblast activation protein inhibitor-04; ¹⁸F-fluorodeoxyglucose; Positron emission tomography/computed tomography; Gastric cancer; Cancer-associated fibroblasts

Core Tip: This prospective pilot study compares ¹⁸F-fibroblast activation protein inhibitor-04 and ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography in 21 gastric cancer (GC) patients. ¹⁸F-fibroblast activation protein inhibitor-04 shows higher uptake, contrast and tumor-burden estimates in primary GC, peritoneal and bone metastases, and higher sensitivity in detecting lymph node and peritoneal metastases, suggesting its potential value for initial staging and postoperative assessment in GC.