Fibroblast Activation Protein-Targeted PET/CT with 18F-Fibroblast Activation Protein Inhibitor-74 for Evaluation of Gastrointestinal Cancer: Comparison with 18F-FDG PET/CT.

Fibroblast activation protein is overexpressed in the stroma of several cancer types. 18F-fibroblast activation protein inhibitor (FAPI)-74 is a PET tracer with high selectivity for fibroblast activation protein and has shown high accumulation in human tumors in clinical studies. However, the use of 18F-FAPI-74 for PET imaging of gastrointestinal cancer has not been systematically investigated. Herein, we investigated the diagnostic accuracy of 18F-FAPI-74 (18F-LNC1005) PET/CT in gastric, liver, and pancreatic cancers and compared the results with those of 18F-FDG PET/CT. Methods: This prospective study analyzed patients with confirmed gastric, liver, or pancreatic malignancies who underwent concurrent 18F-FDG and 18F-FAPI-74 PET/CT between June 2022 and December 2022. PET/CT findings were confirmed by histopathology or radiographic follow-up. 18F-FDG and 18F-FAPI-74 uptake and tumor-to-background ratios were compared using the Wilcoxon signed-rank test. The McNemar test was used to compare the diagnostic accuracy of the 2 scans. Results: Our cohort consisted of 112 patients: 49 with gastric cancer, 39 with liver cancer, and 24 with pancreatic cancer. Among them, 69 patients underwent PET/CT for initial staging and 43 for recurrence detection. Regarding lesion-based diagnostic accuracy, 18F-FAPI-74 PET/CT showed higher sensitivity than did 18F-FDG in the detection of primary tumors (gastric cancer, 88% [22/25] vs. 60% [15/25], P = 0.016; liver cancer, 100% [22/22] vs. 82% [18/22], P = 0.125; pancreatic cancer, 100% [22/22] vs. 86% [19/22], P = 0.250), local recurrence (92% [23/25] vs. 56% [14/25]; P = 0.021), involved lymph nodes (71% [41/58] vs. 40% [23/58]; P < 0.001), and bone and visceral metastases (98% [350/358] vs. 47% [168/358]; P < 0.001). Compared with 18F-FDG, 18F-FAPI-74 PET/CT upstaged 17 patients' TNM staging among all treatment-naïve patients (17/69, 25%) and changed the clinical management of 4 patients (4/43, 9%) in whom recurrence or metastases were detected. Conclusion: 18F-FAPI-74 PET/CT is superior to 18F-FDG PET/CT in detecting primary tumors, local recurrence, lymph node involvement, and bone and visceral metastases in gastric, pancreatic, and liver cancers, with higher uptake in most primary and metastatic lesions.

Acute Appendicitis Complicated by Septic Thrombophlebitis of the Portal Vein Shown by 18 F-FDG and 68 Ga-FAPI-46 PET/CT.

ABSTRACT: Septic thrombophlebitis of the portal vein is a serious infectious disorder and is difficult to be diagnosed at an early stage. In this case, we presented 18 F-FDG and 68 Ga-FAPI-46 PET/CT findings in a 45-year-old man with acute appendicitis complicated by septic thrombophlebitis of the portal vein. 68 Ga-FAPI-46 PET/CT showed intense radiotracer uptake in the thrombosis of the portal vein, with higher SUV max and larger disease extent than 18 F-FDG PET/CT. This case demonstrated that 68 Ga-FAPI PET/CT may be a useful imaging modality for the diagnosis of this infectious condition.

Visualization of Intermetastatic Heterogeneity in Mixed Neuroendocrine Carcinoma-Acinar Adenocarcinoma of the Prostate by 68 Ga-PSMA, 68 Ga-FAPI, and 18 F-FDG PET/CT.

ABSTRACT: Mixed neuroendocrine carcinoma-acinar carcinoma is an uncommon histological type of neuroendocrine prostate cancer. It has been rarely reported in de novo prostate malignancies. In this case, we present 68 Ga-PSMA (prostate-specific membrane antigen), 68 Ga-FAPI, and 18 F-FDG PET/CT findings in the de novo form of mixed large-cell neuroendocrine carcinoma-acinar adenocarcinoma of the prostate. Different levels of radiotracer uptake were observed in different metastatic sites on 68 Ga-PSMA, 68 Ga-FAPI, and 18 F-FDG PET/CT. This case demonstrates that the multitracer PET/CT strategy may be used for the noninvasive detection of the intermetastatic heterogeneity in metastatic neuroendocrine prostate cancer.

68 Ga-FAPI Versus 18 F-FDG PET/CT in the Evaluation of Epithelioid Hemangioendothelioma of Bone.

ABSTRACT: Epithelioid hemangioendothelioma (EHE) is a rare type of vascular tumor that may arise in bone. Here we presented a 62-year-old man with suspected bone metastases who underwent PET/CT to detect the primary tumor. He underwent 18 F-FDG and 68 Ga-FAPI PET/CT under the prospective trial NCT04416165. Radiotracer uptake was much higher with 68 Ga-FAPI PET/CT than with 18 F-FDG PET/CT in most of bone lesions. No intense uptake likely presenting the primary tumor was observed. Subsequent bone biopsy confirmed the diagnosis of EHE of bone. This case suggested that 68 Ga-FAPI PET/CT might be a useful tool for evaluation of EHE.

PET Imaging of Fibroblast Activation Protein in Various Types of Cancer Using 68Ga-FAP-2286: Comparison with 18F-FDG and 68Ga-FAPI-46 in a Single-Center, Prospective Study.

PET imaging that targets fibroblast activation protein (FAP) on the surface of cancer-associated fibroblasts has yielded promising tumor diagnostic results. FAP-2286 contains cyclic peptides as FAP-binding motifs to optimize tumor retention compared with the small-molecule FAP inhibitor (FAPI) series (FAPI-04/46). The aim of this study was to evaluate the diagnostic accuracy of 68Ga-FAP-2286 to detect primary and metastatic lesions in patients with various types of cancer, compared with 18F-FDG and 68Ga-FAP-2286. Methods: Sixty-four patients with 15 types of cancer underwent 68Ga-FAP-2286 PET/CT for initial assessment or detection of recurrence. For comparison, 63 patients underwent paired 68Ga-FAP-2286 and 18F-FDG PET/CT and 19 patients underwent paired 68Ga-FAP-2286 and 68Ga-FAPI-46 PET/CT. Lesion uptake was quantified as SUVmax and tumor-to-background ratio. The Wilcoxon matched-pairs signed-rank test was used to compare SUVmax between PET modalities, and the McNemar test was used to compare lesion detectability. Results: Uptake of 68Ga-FAP-2286 was significantly higher than that of 18F-FDG in primary tumors (median SUVmax, 11.1 vs. 6.9; P < 0.001), lymph node metastases (median SUVmax, 10.6 vs. 6.2; P < 0.001), and distant metastases, resulting in improved image contrast and lesion detectability. All primary tumors (46/46) were clearly visualized by 68Ga-FAP-2286 PET/CT, whereas 9 of the 46 lesions could not be visualized by 18F-FDG PET/CT. The lesion detection rate of 68Ga-FAP-2286 PET/CT was superior to that of 18F-FDG PET/CT for involved lymph nodes (98% [105/107] vs. 85% [91/107], P = 0.001) and bone and visceral metastases (95% [162/171] vs. 67% [114/171], P < 0.001). 68Ga-FAP-2286 yielded tumor uptake and lesion detection rates similar to those of 68Ga-FAPI-46 in a subcohort of 19 patients. Conclusion: 68Ga-FAP-2286 is a promising FAP-inhibitor derivative for safe cancer diagnosis, staging, and restaging. It may be a better alternative to 18F-FDG for the cancer types that exhibit low-to-moderate uptake of 18F-FDG, which include gastric, pancreatic, and hepatic cancers. In addition, 68Ga-FAP-2286 and 68Ga-FAPI-46 yielded comparable clinical results.

Comparison of [68Ga]Ga-FAPI and [18F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study.

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.

68 Ga-FAPI PET/CT Detected Non-PSMA/FDG-Avid Primary Tumor in De Novo Metastatic Prostate Cancer.

ABSTRACT: 68 Ga-labeled PET tracer targeting PSMA is a promising diagnostic approach for staging and restating of prostate cancer (PCa), but cases with clinically relevant PCa and false-negative PSMA PET/CT have been reported. In this case, we reported 68 Ga-PSMA, 18 F-FDG, and 68 Ga-FAPI PET/CT findings in a 65-year-old man with de novo metastatic PCa. 68 Ga-FAPI PET/CT detected non-PSMA/FDG-avid primary PCa, consisting with multiparametric MRI findings. The subsequent histopathologic examination confirmed a Gleason 4 + 5 PCa. This case highlighted that 68 Ga-FAPI PET/CT may be a useful imaging modality for primary PCa detection and localization.

Serous Cystadenoma of the Pancreas Showing Increased Uptake on 68 Ga-FAPI PET/CT.

ABSTRACT: Serous cystadenoma of the pancreas is a type of pancreatic cystic neoplasm frequently found in clinical practice. Serous cystadenoma of the pancreas can have a varied morphological presentation on imaging examinations. Therefore, it is sometimes very challenging to differentiate serous cystadenoma of the pancreas from pancreatic malignancy. In this study, we present a case of serous cystadenoma of the pancreas showing focally elevated radiotracer uptake on 68 Ga-FAPI PET/CT. Considering potential future clinical use of 68 Ga-FAPI PET/CT in malignancy, awareness of the false-positive findings is important for the differential diagnosis and management of these lesions.

Epiglottic Polymorphous Adenocarcinoma With Multiple Bone Metastases Detected by 68 Ga-FAPI PET/CT.

ABSTRACT: Polymorphous adenocarcinoma (PAC) is generally an indolent tumor that mostly commonly affects the minor salivary gland. Polymorphous adenocarcinoma with distant metastases is extremely rare. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT imaging findings in a rare case of epiglottic PAC with multiple bone metastases. 68 Ga-FAPI PET/CT showed superiority over 18 F-FDG PET/CT for detecting the primary and metastatic PAC. This case highlighted that 68 Ga-FAPI may be a promising radiopharmaceutical in the diagnosis of PAC, especially for detecting the PACs arising in uncommon sites.

Uncommon Metastases From Occult Breast Cancer Revealed by 18 F-FDG and 68 Ga-FAPI PET/CT.

ABSTRACT: Metastases to gastrointestinal tract from breast cancer are very rare and can be diagnostically challenging. In this case, we reported 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 54-year-old women with such uncommon metastases from breast cancer. Although the primary tumor of breast cancer remained radiologically occult, 68 Ga-FAPI PET/CT showed a far better tumor-to-background ratio than 18 F-FDG PET/CT for detecting the metastatic lesions, especially for detecting the retroperitoneal lymph node and rectal metastases.

Differentiation of Reactive Lymph Nodes and Tumor Metastatic Lymph Nodes With 68Ga-FAPI PET/CT in a Patient With Squamous Cell Lung Cancer.

ABSTRACT: False-positive findings of mediastinal lymph node often confound the image interpretation of the preoperative PET/CT in non-small cell lung cancer. In this case, we reported 18F-FDG and 68Ga-FAPI PET/CT findings in a patient with squamous cell lung cancer. 18F-FDG-based TNM stage was stage IIIA (T1bN2M0) due to increased uptake in the enlarged right lower paratracheal lymph node. However, no abnormal 68Ga-FAPI uptake was observed in this lymph node. Subsequent histopathological examination revealed no evidence of malignancy in the mediastinal lymph nodes. Therefore, the tumor stage was downstaged to stage IA (T1bN0M0), which was in accordance with 68Ga-FAPI-based TNM stage.

68Ga-DOTATATE PET/CT in Primary Pulmonary Lymphoepithelioma-Like Carcinoma.

ABSTRACT: Primary pulmonary lymphoepithelioma-like carcinomas (LELCs) are extremely rare tumors with better prognosis than other types of lung malignancies. In this case, we present 18F-FDG and 68Ga-DOTATATE PET/CT findings in a 52-year-old woman with pathologically confirmed pulmonary LELC. The pulmonary LELC presented mild 18F-FDG but avid 68Ga-DOTATATE uptake, indicating that the somatostatin receptor 2 may be highly expressed in LELCs. Therefore, 68Ga-DOTATATE PET/CT is a useful tool for tumor detection and initial staging in patients with LELCs.

18F-FDG Versus 68Ga-FAPI PET/CT in Visualizing Primary Hepatic Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue.

ABSTRACT: The prevalence of primary hepatic mucosa-associated lymphoid tissue lymphomas is extremely low. In this case, we present 18F-FDG and 68Ga-FAPI PET/CT findings in a 76-year-old man with pathologically confirmed primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. 68Ga-FAPI PET/CT showed a better tumor-to-background ratio than 18F-FDG PET/CT in the hepatic lesion because there is little 68Ga-FAPI uptake in the liver parenchyma. This case indicates that 68Ga-FAPI PET/CT may be an alternate method for evaluating hepatic involvement of lymphoma, especially for the non-FDG-avid lymphomas.

68Ga-Exendin-4 PET/CT Differentiates Insulinoma From Accessory Spleen in a Patient Presenting Indeterminate MRI and 68Ga-DOTATATE PET/CT Findings.

ABSTRACT: A 55-year-old woman with endogenous hyperinsulinemia hypoglycemia was clinically diagnosed with insulinoma. Contrast-enhanced MRI revealed an inconclusive hypointense lesion in the pancreatic tail, and the enhancement pattern does not support the diagnosis of insulinoma. 68Ga-DOTATATE PET/CT showed intense radioactivity in this nodule, similar to the radioactivity of the adjacent spleen. Therefore, the diagnosis of accessory spleen cannot be excluded. Follow-up with 68Ga-exendin-4 PET/CT also showed intense uptake in this nodule, but no significant uptake in the spleen was observed at this time. Therefore, the insulinoma was unmasked from the spleen, excluding the diagnosis of accessory spleen, and allowing curative surgery.

Positron emission tomography and computed tomography with [68Ga]Ga-fibroblast activation protein inhibitors improves tumor detection and staging in patients with pancreatic cancer.

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.

18F-FDG and 68Ga-FAPI PET/CT in the Evaluation of Ground-Glass Opacity Nodule.

ABSTRACT: A 50-year-old woman with a newly detected pulmonary ground-glass opacity (GGO) nodule underwent PET/CT to determine the likelihood of malignancy. This patient was enrolled in the prospective study (NCT04588064) to determine the effectiveness of 18F-FDG and 68Ga-FAPI PET/CT for characterization of the GGO nodule. On PET/CT images, minimal 18F-FDG uptake but intense 68Ga-FAPI uptake was observed in this GGO nodule. This patient subsequently underwent video-assisted thoracoscopic surgery, and postoperative pathological examination confirmed the diagnosis of invasive adenocarcinoma. This case presented an example where 68Ga-FAPI PET/CT showed higher tracer uptake than 18F-FDG in the malignant GGO nodule.