Asia Oceania Journal of Nuclear Medicine and Biology

Asia Oceania Journal of Nuclear Medicine and Biology

68Ga-FAPI PET/CT in diagnosis, staging and management of gastric carcinoma: A systematic review and meta-analysis

Document Type : Meta-Analysis

Authors
Nitin Gupta 1
Partha S Choudhury 2
Amit Rana 3
1 Department of nuclear medicine, Dr Rajendra Prasad Government Medical College and Hospital, Tanda, Kangra, Himachal Pradesh, India
2 Department of nuclear medicine, RGCIRC New Delhi, India
3 Department of oncology, Dr Rajendra Prasad Government Medical College and Hospital, Tanda, Kangra,Himachal Pradesh, India
10.22038/aojnmb.2026.93248.1690
Abstract
Objective(s): Gastric carcinoma is a major cause of cancer related mortality worldwide. Accurate staging, including detection of nodal and distant metastases, is essential for treatment planning. Conventional 18F-FDG PET/CT has important limitations in gastric cancer, especially in diffuse and mucinous histologic subtypes. Fibroblast activation protein inhibitor (FAPI) PET/CT targets cancer-associated fibroblasts and may improve lesion conspicuity.To systematically review and meta-analyse the diagnostic performance of 68Ga-FAPI PET/CT for staging of gastric carcinoma and, in studies with head-to-head data, to compare it with 18F-FDG PET/CT.
Methods: This review followed PRISMA 2020 recommendations. The protocol was prospectively registered in PROSPERO (CRD420251056976). PubMed, EMBASE, Web of Science and Cochrane libraries were searched from January 2016 to December 2023 for clinical studies evaluating 68Ga-FAPI PET/CT in histologically confirmed gastric carcinoma. Two reviewers independently screened records, extracted data, and assessed risk of bias using QUADAS-2. For 68Ga-FAPI PET/CT, per patient 2×2 tables were constructed for detection of primary tumors and metastatic sites. Pooled sensitivity, specificity, positive and negative predictive values and accuracy were estimated using random effects models. Summary ROC (SROC) and hierarchical SROC (HSROC) curves were generated. Comparative analyses with 18F-FDG PET/CT were restricted to studies with head to head data in the same patient cohort, and areas under the curve (AUCs) were compared with DeLong’s test.
Results: Fourteen studies (661 patients) were included; nine provided head to head comparisons with 18F-FDG PET/CT. For detection of primary gastric carcinoma with 68Ga-FAPI PET/CT, pooled sensitivity and specificity were 95-96% and 93% respectively, with an AUC of 0.96 (95% CI ~ 0.89-1.00). For metastatic disease, pooled accuracy for lymph node, omental, visceral and skeletal metastases ranged from ~89% to 97%. In head to head studies, 68Ga-FAPI PET/CT showed higher AUCs than 18F-FDG PET/CT for primary tumors (0.96 vs 0.76; p=0.001) and omental metastases (0.97 vs 0.78; p=2.6×10⁻⁵). Heterogeneity was moderate for most outcomes. Funnel plots and trim and fill analyses suggested possible small study effects, but adjusted pooled diagnostic odds ratios remained high.
Conclusions: 68Ga-FAPI PET/CT demonstrates high diagnostic accuracy for staging of gastric carcinoma and appears to outperform 18F-FDG PET/CT in many settings, particularly for omental and some visceral metastases and for histologic subtypes with low FDG avidity. These findings support the use of 68Ga-FAPI PET/CT as a promising complementary imaging modality for staging and restaging, but not as a stand-alone diagnostic test. Larger, prospective multicentre studies with standardized protocols are required before routine guideline incorporation.
Keywords
Gastric carcinoma
68Ga-FAPI
PET/CT
Fibroblast activation protein Staging
Meta-analysis
Subjects
1.    Kratochwil C, Flechsig P, Lindner T, Abderrahim L, Altmann A, Mier W, Adeberg S, et al. 68Ga-FAPI PET/CT: tracer uptake in 28 different kinds of cancer. Journal of Nuclear Medicine. 2019; 60(6): 801-5. 
2.    Loktev A, Lindner T, Mier W, Debus J, Altmann A, Jäger D, et al. A tumor-imaging method targeting cancer-associated fibroblasts. Journal of Nuclear Medicine. 2018; 59(9):1423-9. 
3.    Smyth EC, Nilsson M, Grabsch HI, van Grieken NC, Lordick F. Gastric cancer. The Lancet. 2020; 396(10251):635-48. 
4.    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68(6): 394-424.
5.       Karimi P, Islami F, Anandasabapathy S, Freedman ND, Kamangar F. Gastric cancer: descriptive epidemiology, risk factors, screening, and prevention. Cancer epidemiology, biomarkers & prevention. 2014; 23(5): 700-13. 
6.       Kawanaka Y, Kitajima K, Fukushima K, Mouri M, Doi H, Oshima T, et al. Diagnostic accuracy of CT for staging of gastric cancer: a systematic review and meta-analysis. Clin Radiol. 2021; 76(10):773-86.
7.    Liu S, He J, Ji C, Guan W, Chen L, et al. MRI for preoperative staging of gastric cancer: a systematic review and meta-analysis. Clin Radiol. 2020; 75(10):786-95.
8.    Al-Batran SE, Homann N, Pauligk C, et al. Histopathological regression in gastric carcinoma after neoadjuvant therapy. J Clin Oncol. 2016; 34(12):1438-44.
9.    Dassen AE, Lips DJ, Hoekstra CJ, et al. FDG-PET in gastric cancer. Eur J Surg Oncol. 2009; 35(6):536-543.
10.Wang S, Zhou X, Xu X, Ding J, Liu S, Hou X, Li N, Zhu H, Yang Z. Clinical translational evaluation of Al 18F-NOTA-FAPI for fibroblast activation protein-targeted tumour imaging. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(13): 4259-71. 
11.Röhrich M, Naumann P, Giesel FL, Choyke PL, Staudinger F, Wefers A, et al. Impact of 68Ga-FAPI PET/CT on staging and therapeutic management in patients with gastro-intestinal cancers. J Clin Oncol. 2021; 39(15 Suppl):e16031.
12.Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68Ga-FAPI and 18F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021; 298(2):393-402.
13.Chen H, Zhao L, Ruan D, Pang Y, Hao B, Dai Y, et al. Usefulness of [68Ga] Ga-DOTA-FAPI-04 PET/CT in patients presenting with inconclusive [18F] FDG PET/CT findings. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(1):73-86. 
14.Giesel FL, Kratochwil C, Lindner T, Marschalek MM, Loktev A, Lehnert W, et al. 68Ga-FAPI PET/CT: biodistribution and preliminary dosimetry estimate of 2 DOTA-containing FAP-targeting agents in patients with various cancers. Journal of Nuclear Medicine. 2019; 60(3): 386-92. 
15.Pang Y, Zhao L, Luo Z, Hao B, Wu H, Lin Q, et al. Comparison of 68Ga-FAPI and 18F-FDG uptake in gastric, duodenal, and colorectal cancers. Radiology. 2021; 298(2):393-402.
16.Chen H, Zhao L, Ruan D, Pang Y, Hao B, Dai Y, et al. Usefulness of [68Ga] Ga-DOTA-FAPI-04 PET/CT in patients presenting with inconclusive [18F] FDG PET/CT findings. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(1): 73-86.
17. Koerber SA, Staudinger F, Kratochwil C, Adeberg S, Haefner MF, Ungerechts G, et al. The role of 68Ga-FAPI PET/CT for patients with malignancies of the lower gastrointestinal tract: first clinical experience. Journal of Nuclear Medicine. 2020; 61(9): 1331-6.
18.Patel CN, Goldsmith SJ, Fisher RE, et al. The role of FAPI PET/CT in detecting gastric adenocarcinoma. Ann Nucl Med. 2019; 33(11):833-41.
19.Gündoğan C, Kömek H, Can C, Yildirim ÖA, Kaplan I, Erdur E, et al. Comparison of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT in the staging and restaging of gastric adenocarcinoma. Nuclear Medicine Communications. 2022; 43(1): 64-72. 
20.Kuten J, Levine C, Shamni O, Pelles S, Wolf I, Lahat G, et al. Head-to-head comparison of [68Ga] Ga-FAPI-04 and [18F]-FDG PET/CT in evaluating the extent of disease in gastric adenocarcinoma. European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49(2): 743-50. 
21.Arçay Öztürk A, Flamen P. FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review. Cancer Imaging. 2023; 23(1):79.
22.Zhang S, Wang W, Xu T, Ding H, Li Y, Liu H, et al. Comparison of diagnostic efficacy of [68Ga] Ga-FAPI-04 and [18F] FDG PET/CT for staging and restaging of gastric cancer. Frontiers in Oncology. 2022; 12: 925100. 
23.Zhao L, Pang Y, Luo Z, Fu K, Yang T, Zhao L, et al. Role of [68Ga] Ga-DOTA-FAPI-04 PET/CT in the evaluation of peritoneal carcino-matosis and comparison with [18F]-FDG PET/CT. European Journal of Nuclear Medicine and Molecular Imaging. 2021; 48(6): 1944-55. 
24.Sun Y, Xu J, Qiao Y, Zhang J, Pan H, Xu X, et al. Assessing the value of 68Ga-FAPI PET/CT in gastric mucinous adenocarcinoma or signet ring cell carcinoma. Radiology: Imaging Cancer. 2024; 6(6): e230195. 
25.Lindner T, Loktev A, Altmann A, Giesel F, Kratochwil C, Debus J, et al. Development of quinoline-based theranostic ligands for the targeting of fibroblast activation protein. Journal of Nuclear Medicine. 2018; 59(9): 1415-22. 
26.   Ballal S, Yadav MP, Moon ES, Kramer VS, Roesch F, Kumari S, et al. First-in-human results on the biodistribution, pharmaco-kinetics, and dosimetry of [177Lu] Lu-DOTA. SA. FAPi and [177Lu] Lu-DOTAGA (SA. FAPi) 2. Pharmaceuticals. 2021; 14(12): 1212.
27.   Zhang L, Yang J, Li X, et al. Fibroblast activation protein imaging in gastric cancer: An early phase clinical trial. Cancer Imaging. 2017; 17(1):12.
28.   Brown K, Williams R, Harris D, et al. Efficacy of 68Ga-FAPI PET/CT versus 18F-FDG PET/CT in detecting peritoneal metastases in gastric cancer. Eur J Radiol. 2021; 142: 109843.
29.   Li C, Tian Y, Chen J, Jiang Y, Xue Z, Xing D, et al. Usefulness of [68Ga] FAPI-04 and [18F] FDG PET/CT for the detection of primary tumour and metastatic lesions in gastrointestinal carcinoma: a comparative study. European Radiology. 2023; 33(4): 2779-91. 
30.   Jones RP, Roberts E, Schofield J, et al. Novel radiotracers for gastric cancer imaging: A systematic review. World J Gastroenterol. 2015; 21(30):8925-36.
31.   Zhang L, Ren G, Huang H, Wang M, Wang X, Zhang J, et al. Utility of [⁶⁸Ga]Ga-FAPI-04 and [¹⁸F]FDG dual-tracer PET/CT in the initial evaluation of gastric cancer. European Radiology. 2023; 33(6):3999–4011.
32.   Lin R, Lin Z, Chen Z, Zheng S, Zhang J, Zang J, et al. [68Ga] Ga-DOTA-FAPI-04 PET/CT in the evaluation of gastric cancer: comparison with [18F] FDG PET/CT. European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49(8): 2960-71. 
33.   Jiang D, Chen X, You Z, Wang H, Zhang X, Li X, et al. Comparison of [68 Ga] Ga-FAPI-04 and [18F]-FDG for the detection of primary and metastatic lesions in patients with gastric cancer: a bicentric retrospective study. European Journal of Nuclear Medicine and Molecular Imaging. 2022; 49(2): 732-42.
Asia Oceania Journal of Nuclear Medicine and Biology
Volume 14, Issue 2
July 2026
Pages 135-150