Utility of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT in the initial evaluation of gastric cancer

European Radiology https://doi.org/10.1007/s00330-022-09321-1 GASTROINTESTINAL Utility of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT in the initial evaluation of gastric cancer Ying Miao 1 & Runhua Feng 2 & Rui Guo 1 & Xinyun Huang 1 & Wangxi Hai 1 & Jian Li 3 & Teng Yu 4 & Qian Qu 1 & Min Zhang 1 & Chengfang Shangguan 5 & Jun Mi 6 & Zhenggang Zhu 2 & Biao Li 1,7 Received: 16 May 2022 / Revised: 29 October 2022 / Accepted: 28 November 2022 # The Author(s) 2022 Abstract Objectives We aimed to investigate the role of [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT for the initial assessment of gastric cancer and to explore the factors associated with their uptake. Methods This study enrolled 62 patients with histopathologically confirmed gastric cancer. We compared the diagnostic performance of [68Ga]FAPI-04, [18F]FDG, and combined dual-tracer PET/CT. The standardized uptake value (SUV) and tumor-tobackground ratio (TBR) were also measured, and the factors that influence tracer uptake were analyzed. Results [68Ga]FAPI-04 PET/CT detected more primary lesions (90.3% vs 77.4%, p = 0.008) and peritoneal metastases (91.7% vs 41.7%, p = 0.031) and demonstrated higher SUVmax and TBR values (p < 0.001) of primary lesions compared to [18F]FDG PET/CT. Dual-tracer PET/CT significantly improved the diagnostic sensitivity for the detection of distant metastases, compared with stand-alone [18F]FDG (97.1% vs 73.5%, p = 0.008) or [68Ga]FAPI-04 (97.1% vs 76.5%, p = 0.016) PET/CT. Subsequently, treatment strategies were changed in nine patients following [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT. Nevertheless, [68Ga]FAPI-04 uptake was primarily influenced by the size and invasion depth of the tumor. Both [68Ga]FAPI-04 and [18F]FDG PET/CT showed limited sensitivity for detecting early gastric cancer (EGC) (37.5% vs 25.0%, p > 0.05). Conclusions In this initial study, [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT were complementary and improved sensitivity for the detection of distant metastases pre-treatment in gastric cancer and could improve treatment stratification in the future. [68Ga]FAPI-04 had limited efficacy in detecting EGC. Key Points • [68Ga]FAPI-04 and [18F]FDG dual-tracer PET/CT are complementary to each other for improving diagnostic sensitivity in the initial evaluation of distant metastases from gastric cancer. • [68Ga]FAPI-04 PET/CT showed limited sensitivity in detecting EGC. • Need for further validation in a larger multi-centre prospective study. Ying Miao, Runhua Feng, Zhenggang Zhu and Biao Li share equal contributions. * Zhenggang Zhu * Biao Li 1 Department of Nuclear Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 2 Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 3 Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 4 Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 5 Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China 6 Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, 280 South Chongqing Road, Shanghai 200025, China 7 Collaborative Innovation Center for Molecular Imaging of Precision Medicine, Ruijin Center, 197 Ruijin Er Road, Shanghai 200025, China European Radiology Keywords Gastric cancer . [68Ga]FAPI-04 . [18F]FDG . PET/CT Abbreviations AGC Advanced gastric cancer EGC Early gastric cancer FAP Fibroblast activation protein FAPI FAP inhibitor IQR Interquartile range MAC Mucinous adenocarcinomas MIP Maximal intensity projection NPV Negative predictive value PCC Poorly cohesive carcinoma PPV Positive predictive value SRCC Signet ring cell carcinomas SUVmax Maximum standardized uptake value SUVmean Mean standardized uptake value TBR Tumor-to-background ratio VOI Volume of interest Introduction Gastric cancer ranks as the fifth and fourth in cancer incidence and cancer-related deaths globally, respectively [1]. Patients are frequently diagnosed with advanced gastric cancer (AGC) due to the insidious early symptoms. Treatment of gastric cancer is currently based on multidisciplinary management, including surgery, systemic chemotherapy, radiotherapy, immunotherapy, and targeted therapy [2]. Accurate evaluation of disease extent is paramount for selecting the appropriate treatment method. [18F]FDG PET/CT imaging for gastric cancer can sometimes be suboptimal, particularly in individuals with non-intestinal-type gastric cancers or individuals with signet ring cell carcinomas (SRCC) or mucinous adenocarcinomas (MAC) [3, 4]. Fibroblast activation protein (FAP) is commonly overexpressed in cancer-associated fibroblasts, which are known to be the primary components of stromal cells that contribute up to 90% of the tumor mass [5, 6]. Recently, 68 Ga-labeled quinoline-based FAP inhibitor (FAPI) has allowed for the imaging of tumor stroma by targeting FAP, among which [68Ga]FAPI-04 has exhibited favorable tumor-to-background ratio (TBR) and kinetics [7, 8]. [ 68 Ga]FAPI-04 PET/CT reportedly outperformed [18F]FDG PET/CT, especially in cancers of unknown primary origin, breast cancer, and several digestive system tumors, including gastric cancer; thus, it may be an alternative to [18F]FDG PET/CT in the detection of these tumors [9, 10]. However, the number of SRCC patients enrolled in previous studies on gastric cancer was limited. Additionally, elevated FAP expression has also been observed during wound healing and matrix remodeling, including chronic inflammation, atherosclerosis, and liver and lung fibrosis [6]. Whether [68Ga]FAPI-04 PET/CT could replace or supplement [18F]FDG PET/CT in the initial evaluation of gastric cancer needs to be further investigated. Based on the comparison of [68Ga]FAPI-04 and [18F]FDG PET/CT in a larger cohort, our research further explored the role of combined dual-tracer PET/CT in the initial assessment of gastric cancer and analyzed the clinicopathological factors that influence tracer uptake. Material and methods Patients The Ruijin Hospital Ethics Committee of Shanghai Jiao Tong University School of Medicine approved this prospective clinical study (2020 CER No.172). This study enrolled 62 patients pathologically diagnosed with gastric cancer by gastroscopy biopsy for initial staging. All patients signed written informed consent prior to PET/CT imaging. Subsequently, [ 68 Ga]FAPI-04 PET/CT and [18F]FDG PET/CT imaging were carried out before treatment. Following comprehensive imaging results, clinical evaluations, and patients’ willingness, 20 patients underwent primary surgery, 25 patients underwent chemotherapy fol (...truncated)