Abstract
Gastric cancer has a high mortality rate when diagnosed at an advanced stage. Since the primary treatment approach is surgery, accurate staging is crucial for treatment management. F-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is the most commonly used molecular imaging method in Nuclear Medicine, employed for staging, evaluation of treatment response, and detection of recurrent disease in gastric cancer. Recently, fibroblast activation protein inhibitors (FAPI) PET/CT imaging has entered the field, showing superior results in gastric cancer. This review discusses the role of molecular imaging modalities in gastric cancer from various perspectives.
References
1Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74:229-263.
2Yang WJ, Zhao HP, Yu Y, et al. Updates on global epidemiology, risk and prognostic factors of gastric cancer. World J Gastroenterol. 2023;29:2452.
3Bell J, Nagtegaal I, Washington M, et al. WHO classification of tumours of the digestive system [Internet]. 5th ed. Board WC of TE, editor. Vol. 13, World Health Organization. 2019. 85-95 p.
4Del Arco CD, Medina LO, Muñoz LE, de las Heras SGG, Aceñero MJF. Is there still a place for conventional histopathology in the age of molecular medicine? Laurén classification, inflammatory infiltration and other current topics in gastric cancer diagnosis and prognosis. Histol Histopathol. 2021;36:587-613.
5Lorenzon L, Omejc M, Hu JK, et al. Difference Between Signet Ring Cell Gastric Cancers and Non-Signet Ring Cell Gastric Cancers: A Systematic Review and Meta-Analysis. Front Oncol. 2021;1:618477.
6Network NCC. Gastric Cancer (Version 1.2022). Version 1.
7Chen Z Da, Zhang PF, Xi HQ, Wei B, Chen L, Tang Y. Recent Advances in the Diagnosis, Staging, Treatment, and Prognosis of Advanced Gastric Cancer: A Literature Review. Front Med. 2021;8:1-12.
8Lordick F, Carneiro F, Cascinu S, et al. Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33:1005-1020.
9Gai QZ, Li XL, Li N, Li L, Meng Z, Chen AF. Clinical significance of multi-slice spiral CT, MRI combined with gastric contrast-enhanced ultrasonography in the diagnosis of T staging of gastric cancer. Clin Transl Oncol. 2021;23:2036-2045.
10Kawanaka Y, Kitajima K, Fukushima K, et al. Added value of pretreatment 18F-FDG PET/CT for staging of advanced gastric cancer: Comparison with contrast-enhanced MDCT. Eur J Radiol. 2016;85:989-995.
11Papanikolaou IS, Triantafyllou M, Triantafyllou K, Rösch T. EUS in the management of gastric cancer. Ann Gastroenterol. 2011;24:9-15.
12Renzulli M, Clemente A, Spinelli D, et al. Gastric Cancer Staging: Is It Time for Magnetic Resonance Imaging? Cancers (Basel). 2020;12:1402.
13Zhang Y, Yu J. The role of MRI in the diagnosis and treatment of gastric cancer. Diagnostic Interv Radiol. 2020;26:176.
14Upadhyay M, Samal J, Kandpal M, Singh OV, Vivekanandan P. The Warburg effect: Insights from the past decade. Pharmacol Ther. 2013;137:318-330.
15Kaneko Y, Murray WK, Link E, Hicks RJ, Duong C. Improving patient selection for 18F-FDG PET scanning in the staging of gastric cancer. J Nucl Med. 2015;56:523-529.
16Altini C, Niccoli Asabella A, Di Palo A, et al. 18F-FDG PET/CT Role in Staging of Gastric Carcinomas: Comparison with Conventional Contrast Enhancement Computed Tomography. Medicine (Baltimore). 2015;94.
17Gertsen EC, Brenkman HJF, Van Hillegersberg R, et al. 18F-Fludeoxyglucose–Positron Emission Tomography/Computed Tomography and Laparoscopy for Staging of Locally Advanced Gastric Cancer: A Multicenter Prospective Dutch Cohort Study (PLASTIC). JAMA Surg. 2021;156:e215340-e215340.
18Jin L, Zhang L, Fu L, Song F, Cheng A. 18F-FDG PET/CT metabolism multi-parameter prediction of chemotherapy efficacy in locally progressive gastric cancer. Ann Nucl Med. 2024;38:475-482.
19Xue XQ, Wang B, Yu WJ, et al. Relationship between total lesion glycolysis of primary lesions based on 18F-FDG PET/CT and lymph node metastasis in gastric adenocarcinoma: A cross-sectional preliminary study. Nucl Med Commun. 2022;43:114-121.
20Kim J, Lim ST, Na CJ, et al. Pretreatment F-18 FDG PET/CT Parameters to Evaluate Progression-Free Survival in Gastric Cancer. Nucl Med Mol Imaging. 2014;48:33-40.
21Wang J, Yu X, Shi A, et al. Predictive value of 18F-FDG PET/CT multi-metabolic parameters and tumor metabolic heterogeneity in the prognosis of gastric cancer. J Cancer Res Clin Oncol. 2023;149:14535-14547.
22Liu G, Hu Y, Cheng X, et al. Volumetric parameters on 18F-FDG PET/CT predict the survival of patients with gastric cancer associated with their expression status of c-MET. BMC Cancer. 2019;19.
23Chen R, Zhou X, Liu J, Huang G. Relationship Between 18 F-FDG PET/CT Findings and HER2 Expression in Gastric Cancer. J Nucl Med. 2016;57:1040-1044.
24Bosch KD, Chicklore S, Cook GJ, et al. Staging FDG PET-CT changes management in patients with gastric adenocarcinoma who are eligible for radical treatment. Eur J Nucl Med Mol Imaging. 2020;47:759-767.
25Schneider PM, Eshmuminov D, Rordorf T, et al. 18FDG-PET-CT identifies histopathological non-responders after neoadjuvant chemotherapy in locally advanced gastric and cardia cancer: cohort study. BMC Cancer. 2018;18.
26Zou H, Zhao Y. 18FDG PET-CT for detecting gastric cancer recurrence after surgical resection: a meta-analysis. Surg Oncol. 2013;22:162-166.
27Kim SJ, Cho YS, Moon SH, et al. Primary TumorF-FDG Avidity Affects the Performance of F-FDG PET/CT for Detecting Gastric Cancer Recurrence. J Nucl Med. 2016;57:544-550.
28Lee JW, Lee SM, Son MW, Lee MS. Diagnostic performance of FDG PET/CT for surveillance in asymptomatic gastric cancer patients after curative surgical resection. Eur J Nucl Med Mol Imaging. 2016;43:881-888.
29Sharma P, Singh H, Suman SKC, et al. 18F-FDG PET-CT for detecting recurrent gastric adenocarcinoma: Results from a Non-Oriental Asian population. Nucl Med Commun. 2012;33:960-966.
30Pernot S, Voron T, Perkins G, Lagorce-Pages C, Berger A, Taieb J. Signet-ring cell carcinoma of the stomach: Impact on prognosis and specific therapeutic challenge. World J Gastroenterol. 2015;21:11428.
31Harada K, Patnana M, Wang X, et al. Low metabolic activity in primary gastric adenocarcinoma is associated with resistance to chemoradiation and the presence of signet ring cells. Surg Today. 2020;50:1223-1231.
32Chon HJ, Kim C, Cho A, et al. The clinical implications of FDG-PET/CT differ according to histology in advanced gastric cancer. Gastric Cancer. 2019;22:113-122.
33Arslan E, Aksoy T, Gündoğan C, et al. Metabolic characteristics and diagnostic contribution of 18F-FDG PET/CT in gastric carcinomas. Mol Imaging Radionucl Ther. 2020;29:25-32.
34Lindner T, Loktev A, Altmann A, et al. Development of Quinoline-Based Theranostic Ligands for the Targeting of Fibroblast Activation Protein. J Nucl Med. 2018;59:1415-1422.
35Loktev A, Lindner T, Mier W, et al. A Tumor-Imaging Method Targeting Cancer-Associated Fibroblasts. J Nucl Med. 2018;59:1423-1429.
36Loktev A, Lindner T, Burger EM, et al. Development of Fibroblast Activation Protein-Targeted Radiotracers with Improved Tumor Retention. J Nucl Med. 2019;60:1421-1429.
37Çermik TF, Ergül N, Yılmaz B, Mercanoğlu G. Tumor Imaging With 68Ga-DOTA-FAPI-04 PET/CT: Comparison With 18F-FDG PET/CT in 22 Different Cancer Types. Clin Nucl Med. 2022;47:e333-e339.
38Kratochwil C, Flechsig P, Lindner T, et al. 68 Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer. J Nucl Med. 2019;60:801-805.
39Shi X, Xing H, Yang X, et al. Comparison of PET imaging of activated fibroblasts and 18F-FDG for diagnosis of primary hepatic tumours: a prospective pilot study. Eur J Nucl Med Mol Imaging. 2021;48:1593-1603.
40Civan C, Kuyumcu S, Has Simsek D, et al. The role of [68 Ga]Ga-FAPI-04 PET/CT in renal cell carcinoma: a preliminary study. Eur J Nucl Med Mol Imaging. 2024;51:852-861.
41Qiu L, Chen Y. 68 Ga-FAPI PET/CT Depicted Non-FDG-Avid Metastatic Appendiceal Mucinous Adenocarcinoma. Radiology. 2021;301:45-45.
42Chen H, Pang Y, Li J, et al. Comparison of [68Ga]Ga-FAPI and [18F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study. Eur Radiol. 2023;33:1329-1341.
43Pang Y, Zhao L, Luo Z, et al. Comparison of 68Ga-FAPI and 18F-FDG Uptake in Gastric, Duodenal, and Colorectal Cancers. Radiology. 2021;298:393-402.
44Fu L, Huang S, Wu H, et al. Superiority of [68Ga]Ga-FAPI-04/[18F]FAPI-42 PET/CT to [18F]FDG PET/CT in delineating the primary tumor and peritoneal metastasis in initial gastric cancer. Eur Radiol. 2022;32:6281-6290.
45Elboga U, Sahin E, Kus T, et al. Comparison of 68Ga-FAPI PET/CT and 18FDG PET/CT Modalities in Gastrointestinal System Malignancies with Peritoneal Involvement. Mol imaging Biol. 2022;24:789-797.
46Kuten J, Levine C, Shamni O, 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. Eur J Nucl Med Mol Imaging. 2022;49:743-750.
47Wang Y, Luo W, Li Y. [68Ga]Ga-FAPI-04 PET MRI/CT in the evaluation of gastric carcinomas compared with [18F]-FDG PET MRI/CT: a meta-analysis. Eur J Med Res. 2023;28:34.
48Miao Y, Feng R, Guo R, et al. Utility of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT in the initial evaluation of gastric cancer. Eur Radiol. 2023;33.
49Liu X, Liu H, Gao C, Zeng W. Comparison of 68Ga-FAPI and 18F-FDG PET/CT for the diagnosis of primary and metastatic lesions in abdominal and pelvic malignancies: A systematic review and meta-analysis. Front Oncol. 2023;13:1093861.
50Lin R, Lin Z, Chen Z, et al. [68Ga]Ga-DOTA-FAPI-04 PET/CT in the evaluation of gastric cancer: comparison with [18F]FDG PET/CT. Eur J Nucl Med Mol Imaging. 2022;49:2960-2971.
51Gündoğan C, Kömek H, Can C, et al. Comparison of 18F-FDG PET/CT and 68Ga-FAPI-04 PET/CT in the staging and restaging of gastric adenocarcinoma. Nucl Med Commun. 2022;43:64-72.
52Liu H, Yang X, Liu L, Qu G, Chen Y. Comparison of 18 F-FDG and 68 Ga-FAPI-04 Uptake in Postoperative Re-evaluation of Gastric, Duodenal, and Colorectal Cancers. Clin Nucl Med. 2023;48:304-308.
53Şahin E, Elboğa U, Çelen YZ, Sever ÖN, Çayırlı YB, Çimen U. Comparison of 68Ga-DOTA-FAPI and 18FDG PET/CT imaging modalities in the detection of liver metastases in patients with gastrointestinal system cancer. Eur J Radiol. 2021;142:109867.
54Du T, Zhang S, Cui XM, et al. Comparison of [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/MRI in the Preoperative Diagnosis of Gastric Cancer. Can J Gastroenterol Hepatol. 2023;2023.
55Qin C, Shao F, Gai Y, et al. 68Ga-DOTA-FAPI-04 PET/MR in the Evaluation of Gastric Carcinomas: Comparison with 18F-FDG PET/CT. J Nucl Med. 2022;63:81-88.
56Xu W, Cai J, Peng T, et al. Fibroblast Activation Protein-Targeted PET/CT with 18F-Fibroblast Activation Protein Inhibitor-74 for Evaluation of Gastrointestinal Cancer: Comparison with 18F-FDG PET/CT. J Nucl Med. 2024;65.
57Baum RP, Schuchardt C, Singh A, et al. Feasibility, Biodistribution, and Preliminary Dosimetry in Peptide-Targeted Radionuclide Therapy of Diverse Adenocarcinomas Using 177 Lu-FAP-2286: First-in-Humans Results. J Nucl Med. 2022;63:415-423.
58Ding J, Qiu J, Hao Z, et al. Prognostic value of preoperative [68 Ga]Ga-FAPI-04 PET/CT in patients with resectable pancreatic ductal adenocarcinoma in correlation with immunohistological characteristics. Eur J Nucl Med Mol Imaging. 2023;50:1780-1791.
59Eshet Y, Tau N, Levanon K, et al. The Role of 68 Ga-FAPI PET/CT in Breast Cancer Response Assessment and Follow-Up. Clin Nucl Med. 2023;48:685-688.
60Miao Y, Feng R, Yu T, et al. Value of 68Ga-FAPI-04 and 18F-FDG PET/CT in Early Prediction of Pathologic Response to Neoadjuvant Chemotherapy in Locally Advanced Gastric Cancer. J Nucl Med. 2024;65:213-220.
61Af Burén S, Tran TA, Klevebro F, Holstensson M, Axelsson R. A 68Ga-FAPI-46 PET/CT Imaging Pitfall in Assessing Residual Gastric Cancer Early After Chemotherapy. Clin Nucl Med. 2022;47:644-645.
62Zhou N, Guo X, Yang M, Zhu H, Yang Z. 68Ga-ZHER2 PET/CT Reveals HER2-Positive Metastatic Gastric Cancer With Better Image Quality Than 18F-FDG. Clin Nucl Med. 2020;45:e101-e102.
63Hernandez MC, Yazaki P, Mortimer JE, et al. Pilot study of HER2 targeted 64Cu-DOTA-tagged PET imaging in gastric cancer patients. Nucl Med Commun. 2023;44:1151-1155.
64Shi D, Xu Z, Cheng Y, et al. 124I-Labeled Immuno-PET Targeting hTREM2 for the Diagnosis of Gastric Carcinoma. Mol Pharm. 2023;20:2235-2244.
