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Objective: In this study, we investigated the role of [68Ga]Ga-FAPI PET imaging in the detection of primary and metastatic gastric signet-ring-cell carcinoma (GSRCC) and compared with [18F]FDG PET. Methods: This retrospective multicenter analysis included 34 patients with histologically confirmed GSRCCs from four medical centers. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. [18F]FDG and [68Ga]Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. McNemar's test was used to compare the diagnostic accuracy between the two techniques. Results: Data were analyzed from 27 paired PET/CT and 7 paired PET/MRI scans for 34 GSRCC patients (16 men and 18 women) who had a median age of 51 years (range: 25–85 years). [68Ga]Ga-FAPI PET showed higher SUVmax and TBR values than did [18F]FDG PET in the primary tumors (SUVmax: 5.2 vs. 2.2, p = 0.001; TBR: 7.6 vs. 1.3, p < 0.001), involved lymph nodes (SUVmax: 6.8 vs. 2.5, p < 0.001; TBR: 5.8 vs. 1.3, p < 0.001), and bone and visceral metastases (SUVmax: 6.5 vs. 2.4, p < 0.001; TBR: 6.3 vs. 1.3, p < 0.001). In diagnostic performance, [68Ga]Ga-FAPI PET exhibited higher sensitivity than [18F]FDG PET for detecting primary tumors (73% [16/22] vs. 18% [4/22], p < 0.001), local recurrences (100% [7/7] vs. 29% [2/7], p = 0.071), lymph node metastases (77% [59/77] vs. 23% [18/77], p < 0.001), and distant metastases (93% [207/222] vs. 39% [86/222], p < 0.001). Conclusion: The results from this multicenter retrospective analysis justify the clinical use of [68Ga]Ga-FAPI tracers for GSRCC diagnosis and staging. Key Points: • [68Ga]Ga-FAPI PET/CT is a promising imaging modality for the detection of primary and metastatic disease and has implications for TNM staging in GSRCC. • In this multicenter study of 34 patients with GSRCC, [68Ga]Ga-FAPI PET exhibited greater radiotracer uptake, tumor-to-background ratios, and diagnostic accuracy than [18F]FDG PET for detecting primary/recurrent tumors and metastatic lesions. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the prognostic value of semiquantitative parameters derived from [68 Ga]Ga-fibroblast activation protein inhibitor (FAPI) PET/CT for patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiotherapy. Methods: We conducted a retrospective analysis on patients from a prospective parent study (NCT04416165). A total of 45 patients with locally advanced ESCC who underwent [68 Ga]Ga-FAPI from December 2019 to March 2021 were included. The maximum standard uptake value (SUVmax), gross tumor volume (GTV), and total lesion-FAPI (TL-FAPI) of the primary tumor were calculated from the corresponding PET/CT image. Unpaired parameters were compared using Student's t test or the Mann–Whitney U test. Paired parameters were compared using the paired t test or the Wilcoxon matched-pairs signed-rank test. Kaplan–Meier curves were generated to calculate progression-free survival (PFS) and overall survival (OS) rates, and Cox regression analysis was performed to determine which PET/CT parameters were prognostic factors for PFS and/or OS. Results: Thirty-four of the 45 patients met the criteria, and the median follow-up time was 24 months (16–29 months). SUVmax-FAPI, GTVFAPI, and TL-FAPI in patients with stage T4 tumors were significantly higher than those in patients with stage T2/T3 tumors (all P < 0.01). In the univariate Cox regression analysis, T stage, N stage, GTVFAPI, and TL-FAPI were associated with PFS, and T stage, GTVFAPI, and TL-FAPI were associated with OS. Upon multivariable analysis, GTVFAPI was an independent prognostic factor for both PFS (hazard ratio (HR), 5.76; 95% confidence interval (CI), 2.13–15.57, P = 0.001) and OS (HR, 4.96; 95% CI, 2.55–18.79, P = 0.001). Conclusion: This pilot study revealed that [68 Ga]Ga-FAPI PET/CT may have prognostic value for patients with ESCC treated with definitive chemoradiotherapy. It may aid in personalized patient management by steering treatment modifications before therapy. Prospective studies with larger samples and longer observation periods are needed. [ABSTRACT FROM AUTHOR]

Purpose: To explore the feasibility of [68Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with non-keratinizing nasopharyngeal carcinoma (NPC) and to evaluate whether [68Ga]Ga-DOTATATE PET/CT could be used for non-invasive determination of somatostatin receptor 2 (SSTR2) expression in NPC. Methods: This prospective study included patients with NPC who underwent [68Ga]Ga-DOTATATE PET/CT between February and May 2021. The [68Ga]Ga-DOTATATE and [18F]FDG uptakes in primary and metastatic NPC lesions were calculated and compared, and the [68Ga]Ga-DOTATATE uptake between SSTR2 score groups was analysed. Results: A total of 36 participants (25 patients, initial staging; 11 patients, recurrence detection) were included; 33 patients also underwent [18F]FDG PET/CT for staging/restaging as a part of their routine diagnostic workup. [68Ga]Ga-DOTATATE PET/CT showed an intense tracer uptake in primary and metastatic NPC lesions. The radiotracer uptake was higher with [68Ga]Ga-DOTATATE than with [18F]FDG PET in primary NPC lesions (SUVmax: 12.03 vs. 10.07, P = 0.048; tumour-to-brain ratio: 36.16 vs. 0.86, P < 0.001) and regional lymph node metastases (median SUVmax: 9.11 vs. 6.12, P < 0.001) and comparable in bone and visceral metastases. Importantly, most NPC lesions showed intense SSTR2 expression (85.7%), which was strongly correlated with the [68Ga]Ga-DOTATATE uptake. The SUVmax of SSTR2-negative lesions was significantly lower than that of SSTR2-positive lesions (SUVmax: 4.95 vs. 12.61, P = 0.013). Conclusion: [68Ga]Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic NPC, with favourable image contrast and comparable diagnostic efficacy when compared to [18F]FDG PET/CT. An intense SSTR2 expression was observed in most NPCs, and this expression was significantly correlated with the [68Ga]Ga-DOTATATE uptake. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the diagnostic performance of [68Ga]Ga-FAPI PET/CT for primary and metastatic pancreatic carcinoma lesions and compare the results with those of [18F]-fluorodeoxyglucose ([18F]FDG) PET/CT. Methods: Patients with suspected or diagnosed pancreatic malignancy, who underwent contemporaneous [18F]FDG and [68Ga]Ga-FAPI PET/CT between June 2020 and January 2021, were retrospectively analyzed. Routine contrast-enhanced CT (CE-CT) is performed in all patients as standardized care. Findings were confirmed by histopathology or radiographic follow-up. We compared radiotracer uptake, diagnostic performance, and TNM (tumor-node-metastasis) classifications. Results: We evaluated 36 participants (25/36 men; median age, 60 years), including 26 patients with pancreatic malignancies and ten patients with pancreatic benign lesions. [68Ga]Ga-FAPI PET/CT showed higher radiotracer uptake and higher sensitivity than [18F]FDG PET/CT in evaluating primary tumors (SUVmax, 21.4 vs. 4.8; sensitivity, 100% vs. 73.1%), involved lymph nodes (SUVmax, 8.6 vs. 2.7; sensitivity, 81.8% vs. 59.1%), and metastases (SUVmax, 7.9 vs. 3.5; sensitivity, 91.5% vs. 44.0%); Compared with [18F]FDG, [68Ga]Ga-FAPI PET/CT upstaged six patients' TNM staging (6/23, 26.1%) and changed two patients' clinical management (2/23, 8.7%). Compared with CE-CT, [68Ga]Ga-FAPI PET/CT upgraded TNM staging in five patients (5/23, 21.7%) and changed the therapeutic regimen in only one patient (1/23, 4.3%). Intense [68Ga]Ga-FAPI uptake was observed throughout the pancreas in 12/26 pancreatic malignancies; dual-time point [68Ga]Ga-FAPI PET/CT may differentiate pancreatitis from malignancy. Conclusions: Compared with [18F]FDG PET/CT, [68Ga]Ga-FAPI PET/CT shows higher sensitivity in detecting primary pancreatic tumors, involved lymph nodes, and metastases and is superior in terms of TNM staging. Prospective trials with larger patient population are needed to evaluate whether [68Ga]Ga-FAPI PET/CT could elicit treatment modification in pancreatic cancer when compared with standard of care imaging. [ABSTRACT FROM AUTHOR]

Objective: Programmed death-ligand 1 (PD-L1) expression status is a crucial index for identifying patients who will benefit from anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy for non-small cell lung cancer (NSCLC). However, the concordance of Tumor Proportion Score (TPS) between biopsies and matched surgical specimens remains controversial. This study aims to evaluate the concordance of PD-L1 expression between image-guided percutaneous biopsies and matched surgical specimens. Method: We evaluated 157 patients diagnosed with operable NSCLC on both surgical tissue sections and matched lung biopsies retrospectively. The patients underwent either regular computed tomography (CT)-guided biopsy (n = 82) or positron emission tomography (PET)/CT-guided biopsy (n = 75). The concordance between surgical specimens and lung biopsies for PD-L1 TPS was evaluated using Cohen's kappa (κ) coefficient. Results: Immunohistochemical expression of PD-L1 was evaluated in both surgical resected specimens and matched biopsies in the eligible 138 patients. The concordance rate of PD-L1 expression between surgical tissue sections and matched biopsies was fairly high at 84.1% (116/138), and the κ value was 0.73 (95% CI: 0.63–0.83, P < 0.001). The concordance rate was higher for tissue sections from PET/CT-guided biopsy than for tissue sections from CT-guided biopsy [88.6% (62/70, κ value: 0.81) vs 79.4% (54/68, κ value: 0.66)]. Conclusion: PD-L1 TPS was strongly concordant between surgical specimens and matched lung biopsies. Thus, the routine evaluation of PD-L1 expression in diagnostic percutaneous biopsies could be reliable for identifying patients who will benefit from anti-PD-1/PD-L1 immunotherapy. [ABSTRACT FROM AUTHOR]

• 68Ga-FAPI PET/CT showed favourable tumour-to-background contrast compared to 18F-FDG PET/CT in oesophageal cancer. • SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with endoscopic examination. • 68Ga-FAPI PET/CT may provide additional information for target volume delineation to avoid tumour geographic misses. To compare 68Ga-fibroblast activation protein inhibitor (FAPI) and 18F-FDG PET/CT in imaging locally advanced oesophageal cancer, and evaluate the potential usefulness of 68Ga-FAPI PET/CT on gross target volume (GTV) delineation aimed at radiotherapy planning for oesophageal cancer as compared with contrast-enhanced CT (CE-CT) and 18F-FDG PET/CT. Twenty-one patients with newly diagnosed oesophageal cancer who underwent both 18F-FDG and 68Ga-FAPI PET/CT scans were selected. GTVs of the primary tumours based on CE-CT (GTV CT), PET/CT, and CE-CT plus PET/CT were delineated. Gross tumour lengths were measured by GTVs and endoscopy and recorded. The 68Ga-FAPI PET showed significantly higher radiotracer uptake than 18F-FDG PET (median SUVmax 16.71 vs. 11.23; P = 0.002) in the primary tumours. SUV thresholds of FAPI ×20%, 30%, 40%, and FDG ×40% showed similar lesion lengths compared with that in endoscopic examination (P > 0.05). GTV CT demonstrated the largest volume (median: 48.80 mm3, range: 14.83–162.23 mm3) than PET-based GTVs. For PET/CT-guided complementary contouring of GTV CT , four patients (19%) were increased by FAPI ×20% and 30%, two patients (9.5%) were increased by FAPI ×40%, and only one patient was increased by FDG ×40%. Furthermore, the volume of GTV based on CE-CT plus FAPI ×20%, 30%, and 40% showed no significant difference with GTV CT and planning target volume based CE-CT plus FAPI-PET and meets the organ at risk standard. The 68Ga-FAPI PET/CT methodology showed favourable tumour-to-background contrast in oesophageal cancer and might provide additional information for target volume delineation and help avoid tumour geographic misses. [ABSTRACT FROM AUTHOR]

Recurrent breast cancer poses considerable diagnostic and therapeutic challenges for clinic. Clinical suspicion of recurrence must be first confirmed by imaging studies. Then re-biopsy of suspected recurrence and metastasis in patients with breast cancer is recommended in the practice guidelines of the National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) to confirm whether the molecular subtype changes. It may change the individual treatment plan directly. Our research provided an integrated algorithm for locally recurrent or distant metastatic breast cancer, including early relapse detection and subsequently a new practical PET/CT imaging guide biopsy approach for surveilling molecular subtype shifts of the recurrent breast cancer. In our results, 18F-FDG PET/CT appears to be more sensitive and accurate than conventional imaging technologies in early detecting locally recurrent or metastatic breast cancer. PET/CT-guided percutaneous FDG-avid target biopsies offers a new integrated precise re-biopsy algorithm for pathologic confirm and surveillance of molecular subtype shifts of the recurrent breast cancer. The precise algorithm for breast cancer recurrence and metastasis can be established in one stop, opening a window of opportunity for breast cancer patients to improve precise individual therapy and prolong survival. [ABSTRACT FROM AUTHOR]