Polysaccharides regulate Th1/Th2 balance: A new strategy for tumor immunotherapy.

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 cells are two key subsets of Th cells that exist in relative equilibrium through the secretion of cytokines that suppress their respective immune response. When the type of cytokine in the tumor microenvironment is altered, this equilibrium may be disrupted, leading to a shift from Th1 to Th2 immune response. Th1/Th2 imbalance is one of the decisive factors in the development of malignant tumors. Therefore, focusing on the balance of Th1/Th2 anti-tumor immune responses may enable future breakthroughs in cancer immunotherapy. Polysaccharides can regulate the imbalance between Th1 and Th2 cells and their characteristic cytokine profiles, thereby improving the tumor immune microenvironment. To our knowledge, this study is the most comprehensive assessment of the regulation of the tumor Th1/Th2 balance by polysaccharides. Herein, we systematically summarized the intrinsic molecular mechanisms of polysaccharides in the regulation of Th1 and Th2 cells to provide a new perspective and potential target drugs for improved anti-tumor immunity and delayed tumor progression.

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.

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.

Fibroblast activation protein-based theranostics in cancer research: A state-of-the-art review.

In recent years, quinoline-based fibroblast activation protein (FAP) inhibitors (FAPI) have shown promising results in the diagnosis of cancer and several other diseases, making them the hotspot of much productive research. This review summarizes the literature for the state-of-the-art FAPI-PET imaging for cancer diagnosis compared with fluorodeoxyglucose (FDG)-PET. We also summarize the use of FAPI-PET for therapeutic regimen improvement and fibroblast activation protein (FAP)-targeted molecule modification strategies, as well as preliminary clinical studies regarding FAP-targeted radionuclide therapy. Our qualitative summary of the literature to date can inform future research directions, medical guidelines, and optimal clinical decision-making.

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.

Use of 68Ga-FAPI PET/CT for Detecting Myeloid Sarcoma of the Breast and Assessing Early Response to Chemotherapy.

ABSTRACT: Myeloid sarcoma is a rare presentation of acute myeloid leukemia as a solid tumor at various extramedullary sites. In this case, we report 18F-FDG and 68Ga-FAPI PET/CT findings in an 18-year-old woman with biopsy-proven myeloid sarcoma involving the left breast. 68Ga-FAPI PET/CT showed a far better tumor-to-background contrast than 18F-FDG PET/CT in the left breast mass. Moreover, follow-up 68Ga-FAPI PET/CT after 2 cycles of chemotherapy revealed a reduction in tumor size with decreasing activity in the myeloid sarcoma lesions.

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.

68Ga-FAPI PET/CT Distinguishes the Reactive Lymph Nodes From Tumor Metastatic Lymph Nodes in a Patient With Nasopharyngeal Carcinoma.

ABSTRACT: Accurate clinical staging is crucial for managing nasopharyngeal carcinoma (NPC). However, false-positive finding of cervical lymph nodes in 18F-FDG PET/CT and MRI may lead to unnecessary chemotherapy for NPC. In this case, we report a patient with NPC who was incorrectly diagnosed with bilateral cervical lymph node metastases by both 18F-FDG PET/CT and MRI. Subsequent pathology results showed proliferating lymphoid cells with no signs of tumor metastasis. Interestingly, no abnormal 68Ga-FAPI uptake was observed in the nonmetastatic reactive lymph nodes. Therefore, 68Ga-FAPI PET/CT may be useful for assessment of pretreatment lymph node status in NPC.

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.

Increased 68Ga-FAPI Uptake in Ankylosing Spondylitis in a Patient With Rectal Cancer.

ABSTRACT: Ankylosing spondylitis represents an inflammatory arthropathy with a predilection for the axial skeleton. We reported 68Ga-FAPI PET/CT finding of ankylosing spondylitis in a 65-year-old patient with rectal cancer. In addition to accumulating in primary tumor and metastatic lymph nodes, increased 68Ga-FAPI uptake was also observed in the sacroiliac and costovertebral joints, indicating sacroiliitis and spondylitis. However, no abnormal 18F-FDG uptake was observed in the inflammatory lesions. This case highlighted that 68Ga-FAPI PET/CT is useful for the evaluation of inflammatory conditions in ankylosing spondylitis.

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-Fibroblast Activation Protein Inhibitor, a Promising Radiopharmaceutical in PET/CT to Detect the Primary and Metastatic Lesions of Chromophobe Renal Cell Carcinoma.

ABSTRACT: 18F-FDG PET/CT was performed to locate the primary lesion in a 71-year-old man with bone metastasis. However, no abnormal 18F-FDG activity likely presenting the primary tumor was observed. 68Ga-fibroblast activation protein inhibitor PET/CT was then performed for further detecting the primary tumor, which showed a higher activity in lesions of bone metastases than 18F-FDG. Additionally, another lesion with intense uptake was observed in the inferior pole of right kidney, likely presenting the primary tumor. A renal biopsy revealed the diagnosis of chromophobe renal cell carcinoma. This case highlighted that 68Ga-fibroblast activation protein inhibitor could be a promising radiopharmaceutical in the diagnosis of renal cell carcinoma.

Comparison of 68Ga-FAPI and 18F-FDG PET/CT in a Patient With Cholangiocellular Carcinoma: A Case Report.

The present study compared Ga-FAPI and F-FDG PET/CT in a patient with cholangiocellular carcinoma. In this case, Ga-FAPI PET shows much higher tumor-to-background contrast of primary tumor and reveals more metastatic lesions, especially the micrometastases of bones, than F-FDG PET.