Comparison of 18 F-FDG and 18 F-FAPI PET/CT Findings of Signet-Ring Cell Carcinoma of the Stomach.

ABSTRACT: A 66-year-old man with gastric signet-ring cell carcinoma underwent both 18 F-FDG and 18 FAl-NOTA-FAPI PET/CT imaging. There was no abnormal FDG activity in the stomach, but there was diffuse intense 18 FAl-NOTA-FAPI uptake in the known lesion and an adjacent metastasis.

Head to head comparison of 68Ga-DOTA-FAPI-04 vs 18F-FDG PET/CT in the evaluation of primary extrapulmonary tumors in the chest.

OBJECTIVE: We conducted a prospective study using 18F-flurodeoxyglucose (18F-FDG) and 68Ga-DOTA-FAPI-04 (fibroblast-activation protein inhibitor, 68Ga-FAPI) PET/CT to diagnose, differentiate, and stage primary extrapulmonary tumors of the thorax. METHODS: Fifty-four participants were undergoing 18F-FDG and 68Ga-FAPI PET/CT and divided into the benign, intermediate, and malignant based on pathology. The maximum standardized uptake value (SUVmax), the tumor-to-blood pool ratio, and tumor-to-liver ratio were compared for primary tumors, lymph nodes, and metastases between the two modalities by two independent samples t tests. One-way ANOVA was used to compare the uptake of 18F-FDG or 68Ga-FAPI among the three groups. RESULTS: Fifty-four participants were confirmed to have 71 primary lesions, 56 metastatic lymph nodes, and 43 metastatic lesions. 18F-FDG PET/CT could both effectively distinguish malignant lesions from non-malignant lesions, accuracies of 87.32% (p < 0.001). 68Ga-FAPI PET/CT effectively differentiated benign lesions from the non-benign, accuracy being 91.55% (p < 0.001). The accuracies of 18F-FDG and 68Ga-FAPI for detecting lymph node metastasis were 77.22% (61/79) and 87.34% (69/79) (p = 0.096). The uptake of 68Ga-FAPI in metastatic lymph nodes was significantly higher than that of the nonmetastatic (p < 0.001). The detection rate of 68Ga-FAPI PET/CT for metastatic lesions was significantly higher than that of 18F-FDG, 100% (43/43) vs. 53.49% (23/43) (p < 0.001). Compared with 18F-FDG PET/CT, 68Ga-FAPI PET/CT changed the treatment strategy of 7.4% (4/54) participants. CONCLUSION: 68Ga-FAPI PET/CT is valuable in the diagnosis and differentiation of primary extrapulmonary tumors and superior to 18F-FDG PET/CT for evaluating lymph node and distant metastasis. CLINICAL RELEVANCE STATEMENT: The application of 68Ga-FAPI PET/CT in primary extrapulmonary chest tumors is valuable, which is reflected in diagnosis, differentiation and exploration of lymph node metastasis and distant metastasis. KEY POINTS: • 68Ga-FAPI PET/CT is valuable in the diagnosis, differentiation, and staging of primary extrapulmonary tumors. • 68Ga-FAPI PET/CT is superior to 18 F-FDG PET/CT for evaluating lymph node and distant metastasis.

Metabolic regulation and antihyperglycemic properties of diet-derived PGG through transcriptomic and metabolomic profiling.

Diabetes has become a significant disease threatening human health and social development. Food intervention is considered an essential strategy to prevent early diabetes development sustainably. The natural product, 1,2,3,4,6-penta-O-galloyl-ß-D-glucose (PGG), commonly found in fruits and diets, has many potential antihypoglycemic, antibacterial, and antitumor activities. We found that PGG can promote glucose uptake in whole-organism zebrafish screening, which help in downregulating the glucose levels. We investigated the metabolome and transcriptome changes in zebrafish exposed to high glucose and PGG intervention. The differential genes and metabolites were screened out based on the comparisons of blank, hyperglycemic, and the PGG-exposed groups of zebrafish larvae. Combined with RT-qPCR validation, we found that PGG mainly restored four genes (fthl27, LOC110438965, plat, and aacs) and six metabolites abnormally invoked by high glucose. These validated genes are related with the key metabolites sphingosine and (R)-3-hydroxybutanoate involving the pathways of apelin, apoptosis, necroptosis, and butanoate metabolism. Our findings provided a new mechanistic basis for understanding the hypoglycaemic function of the commonly present dietary molecule (PGG) and offered a new perspective for the rational utilization of PGG to regulate metabolic disorders.

Amygdalin alleviated TGF-ß-induced epithelial-mesenchymal transition in bronchial epithelial cells.

OBJECTIVE: Transforming growth factor-beta TGF-ß-induced epithelial-mesenchymal transition (EMT) in bronchial epithelial cells contributes to airway wall remodeling in asthma. This study aims to explore the role of amygdalin, an active ingredient in bitter almonds, in TGF-ß-induced EMT in bronchial epithelial cells and to elucidate the possible mechanisms underlying its biological effects. METHODS: An asthmatic mouse model was established through ovalbumin induction. Primary mouse bronchial epithelial cells and a human bronchial epithelial cell line were incubated with transforming growth factor-beta (TGF-ß) to induce EMT, whose phenotype of cells was evaluated by the expressions of EMT markers [alpha-smooth muscle actin (α-SMA), vimentin, and fibronectin] and cell migration capacity. A co-immunoprecipitation assay was performed to assess the ubiquitination of heparanase (HPSE). RESULTS: In asthmatic model mice, amygdalin treatment relieved airway wall remodeling and decreased expressions of EMT markers (α-SMA and vimentin). In TGF-ß-treated bronchial epithelial cells, amygdalin treatment decreased the mRNA and protein levels of EMT markers (α-SMA, vimentin, and fibronectin) without impairing cell viability. Through the Swiss Target Prediction database, HPSE was screened as a candidate downstream target for amygdalin. HPSE overexpression further promoted TGF-ß-induced EMT while the HPSE inhibitor suppressed TGF-ß-induced EMT in bronchial epithelial cells. In addition, HPSE overexpression reversed the inhibitory effect of amygdalin on TGF-ß-induced EMT in bronchial epithelial cells. The following mechanism exploration revealed that amygdalin downregulated HPSE expression by enhancing ubiquitination. CONCLUSION: Our study showed that amygdalin inhibited TGF-ß-induced EMT in bronchial epithelial cells and found that the anti-EMT activity of amygdalin might be related to its regulatory effect on HPSE expression.

Predictive Value of 18 F-FDG PET/MRI for Pleural Invasion in Solid and Subsolid Lung Adenocarcinomas Smaller Than 3 cm.

BACKGROUND: Positron emission tomography (PET)/MRI combines the characteristics of metabolism imaging and high soft tissue resolution, and could provide high diagnostic efficacy for assessment of pleural invasion (PI) of lung cancer. PURPOSE: To investigate the application of 18 F-fluorodeoxyglucose (FDG) PET/MRI for predicting PI of lung cancer with the maximum diameter ≤3 cm. STUDY TYPE: Prospective. POPULATION: A total of 44 patients with non-small cell lung cancer (NSCLC), age from 39 to 79 years old, including 19 (56.82%) females. FIELD STRENGTH/SEQUENCE: A 3-T, hybrid PET/MRI including axial fast spin echo respiratory-triggered T2 fat-suppressed imaging (T2FS) and echo planar imaging diffusion-weighted imaging (DWI). ASSESSMENT: The maximum standardized uptake value (SUVmax) of all lesions was measured on PET images. Localized effusion outside the contact between the nodules and the pleura on T2FS and signal at the contact between the nodules and the pleura on DWI were evaluated by experienced physicians through visual assessment of the MRI sequences. STATISTICAL TESTS: Three models (models 1-3) were developed, incorporating CT, CT and PET, PET and MRI features, and Lasso regression was used in feature selection. The receiver operating characteristic (ROC) curve for PI diagnosis was visualized for each model, and the area under the curve (AUC) was calculated. The DeLong test was used to compare the different AUCs. A P value < 0.05 was considered statistically significant. RESULTS: The AUC of models 1-3 was 0.762, 0.829, and 0.915, respectively. The DeLong test showed a statistically significant difference between the AUCs of model 1 vs. model 3, while the differences between the AUCs of model 1 vs. model 2 (P = 0.253) and model 2 vs. model 3 (P = 0.075) were not statistically significant. DATA CONCLUSION: 18 F-FDG PET/MRI might show high predictive value for lung adenocarcinoma smaller than 3 cm with PI. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

18F-FDG distribution pattern improves the diagnostic accuracy of single pulmonary solid nodule.

Background: The main purpose is to explore the use of visual assessment of the heterogeneous distribution of 18F-FDG in single pulmonary solid lesions to differentiate the benign from the malignant. Methods: The 200 cases of pulmonary nodules or masses examined by 18F-FDG PET/CT were retrospectively analyzed. The heterogeneity of 18F-FDG distribution of the lesion was visually and quantitatively evaluated and the higher part of metabolism was observed and measured at the proximal or distal part to determine the lesion nature. The sensitivity, specificity, PPV, NPV, and accuracy of this method were calculated. Results: Total 171 pulmonary lesions showed heterogeneity of 18F-FDG uptake, including the 111 malignant and 60 benign. 54/60 (90.00%) benign lesions showed higher 18F-FDG uptake visually at distal part, while 104/111 (93.69%) malignant lesions showed higher 18F-FDG uptake visually at the proximal part. This visual method has good repeatability with a high kappa value (0.821, p<0.001). 52/60 (86.67%) benign lesions showed higher 18F-FDG uptake quantitatively at distal part, while 107/111 (96.40%) malignant lesions showed higher 18F-FDG uptake quantitatively at the proximal part. The sensitivity, specificity, PPV, NPV and accuracy of visual and quantitative methods were 93.69%; 96.40%, 90.0%; 86.67%, 94.55%; 93.04%, 88.52%; 92.86%, 92.40%; 92.98%, respectively (p<0.001). When combining the metabolic value and morphological characteristics of PET/CT with visual 18F-FDG heterogeneous features, the accuracy reached to 98.25%. The other 29 lesions (14.5%) with no heterogeneity were smaller (2.17 ± 1.06 vs 3.58 ± 1.48, P<0.001). Conclusions: Benign and malignant lung lesions showed different heterogeneity of 18F-FDG uptake. Lung cancer can be effectively distinguished from infectious or inflammatory lesions by this simple and convenient method.

Head­to­head assessment of [68Ga]Ga-DOTA-FAPI-04 PET/CT vs [18F]FDG PET/CT in fibroblastic tumors.

OBJECTIVES: We aimed to evaluate [68Ga]Ga-DOTA-FAPI-04 versus [18F]FDG PET/CT in the application of fibroblastic tumors. METHODS: Twenty participants with 6 subtypes of fibroblastic tumors prospectively underwent 18F-FDG and [68Ga]Ga-DOTA-FAPI-04 PET/CT examinations to evaluate the lesions. PET/CT findings were confirmed by surgical pathology of fifteen participants, puncture biopsy of two participants, or imaging follow-up of three participants. Two independent sample t tests were used to compare the uptake of [18F]FDG vs [68Ga]Ga-DOTA-FAPI-04 in primary, recurrent and metastatic lesions. One-way ANOVA was used to compare the uptake of [18F]FDG or [68Ga]Ga-DOTA-FAPI-04 among primary, recurrent, and metastatic lesions. The uptake of [68Ga]Ga-DOTA-FAPI-04 vs [18F]FDG in different histopathological lesions was compared by two independent sample t tests. RESULTS: Twenty participants were confirmed to have 38 lesions. Although there was no significant difference in the detection of lesions between [68Ga]Ga-DOTA-FAPI-04 and [18F]FDG PET/CT (38 vs 36, p = 0.493), the uptake of [68Ga]Ga-DOTA-FAPI-04 in lesions was significantly higher than that of [18F]FDG (p < 0.001), including primary (p < 0.001), recurrent (p = 0.018) and metastatic (p < 0.001) lesions. The SUVmax of [68Ga]Ga-DOTA-FAPI-04 in primary and recurrent lesions was higher than that in metastasis (p = 0.034 and p = 0.015, respectively). The SUVmax of [68Ga]Ga-DOTA-FAPI-04 in primary and recurrent malignant lesions was significantly higher than that of the intermediate (p < 0.001). The SUVmax of [68Ga]Ga-DOTA-FAPI-04 in one participant of recurrent SFT with 5 lesions was significantly lower after treatment than before treatment (p = 0.016). CONCLUSIONS: [68Ga]Ga-DOTA-FAPI-04 outperformed [18F]FDG PET/CT in displaying the primary, recurrent and metastatic lesions of fibroblastic tumors.

LC-MS/MS Insight into Vitamin C Restoration to Metabolic Disorder Evoked by Amyloid ß in Caenorhabditis elegans CL2006.

The transitional expression and aggregation of amyloid ß (Aß) are the most important causative factors leading to the deterioration of Alzheimer's disease (AD), a commonly occurring metabolic disease among older people. Antioxidant agents such as vitamin C (Vc) have shown potential effects against AD and aging. We applied an liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method and differential metabolites strategy to explore the metabolic disorders and Vc restoration in a human Aß transgenic (Punc-54::Aß1-42) nematode model CL2006. We combined the LC-MS/MS investigation with the KEGG and HMDB databases and the CFM-ID machine-learning model to identify and qualify the metabolites with important physiological roles. The differential metabolites responding to Aß activation and Vc treatment were filtered out and submitted to enrichment analysis. The enrichment showed that Aß mainly caused abnormal biosynthesis and metabolism pathways of phenylalanine, tyrosine and tryptophan biosynthesis, as well as arginine and proline metabolism. Vc reversed the abnormally changed metabolites tryptophan, anthranilate, indole and indole-3-acetaldehyde. Vc restoration affected the tryptophan metabolism and the biosynthesis of phenylalanine, tyrosine and tryptophan. Our findings provide supporting evidence for understanding the metabolic abnormalities in neurodegenerative diseases and the repairing effect of drug interventions.

Fluidic innervation sensorizes structures from a single build material.

Multifunctional materials with distributed sensing and programmed mechanical properties are required for myriad emerging technologies. However, current fabrication techniques constrain these materials' design and sensing capabilities. We address these needs with a method for sensorizing architected materials through fluidic innervation, where distributed networks of empty, air-filled channels are directly embedded within an architected material's sparse geometry. By measuring pressure changes within these channels, we receive feedback regarding material deformation. Thus, this technique allows for three-dimensional printing of sensorized structures from a single material. With this strategy, we fabricate sensorized soft robotic actuators on the basis of handed shearing auxetics and accurately predict their kinematics from the sensors' proprioceptive feedback using supervised learning. Our strategy for facilitating structural, sensing, and actuation capabilities through control of form alone simplifies sensorized material design for applications spanning wearables, smart structures, and robotics.

Higher accuracy of [68 Ga]Ga-DOTA-FAPI-04 PET/CT comparing with 2-[18F]FDG PET/CT in clinical staging of NSCLC.

PURPOSE: This study aimed to explore the clinical staging performance of [68 Ga]Ga-DOTA-FAPI-04 PET/CT compared with that of 2-[18F]FDG PET/CT in non-small cell lung cancer (NSCLC) patients lesion by lesion. METHODS: A total of 134 diagnosed or suspected NSCLC patients were enrolled in the prospective study (ChiCTR2000038080); they received paired 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT. Of these patients, the retrospective analysis of 74 NSCLC patients with pathological results was conducted from primary tumor (T) diagnosis, lymph node (N), and metastatic lesion (M) staging. The imaging characteristics of the lung nodules and suspected metastases were obtained and analyzed, and the staging performance of 2-[18F]FDG PET/CT and [68 Ga]Ga-DOTA-FAPI-04 PET/CT was compared. RESULTS: For T diagnosis, [68 Ga]Ga-DOTA-FAPI-04 showed better diagnostic performance than 2-[18F]FDG in 79 lung nodules of 72 patients, especially for nonsolid and small-dimension adenocarcinoma nodules. For N staging, 98 lymph nodes (LNs) with pathological results in 37 patients were analyzed. The SUVmax of [68 Ga]Ga-DOTA-FAPI-04 in the nonmetastatic LNs was significantly lower than that in the metastatic LNs. Regarding metastatic LN identification, the calculated optimum cut-off value of [68 Ga]Ga-DOTA-FAPI-04 SUVmax was 5.5, and the diagnostic accuracy using [68 Ga]Ga-DOTA-FAPI-04 and 2-[18F]FDG criteria was 94% and 30%, respectively (P < 0.001). For M staging, [68 Ga]Ga-DOTA-FAPI-04 identified more lesions than 2-[18F]FDG (257 vs. 139 lesions) in 14 patients with multiple metastases. Overall, the staging accuracy of [68 Ga]Ga-DOTA-FAPI-04 was better than that of 2-[18F]FDG in 52 patients with different pathological stages [43/52 (82.7%) vs. 27/52 (51.9%), P = 0.001]. CONCLUSION: Compared with 2-[18F]FDG PET/CT, [68 Ga]Ga-DOTA-FAPI-04 PET/CT demonstrated better staging performance in NSCLC patients with different pathological stages, especially those with localized disease.

The 68 Ga-DOTA-FAPI-04 PET/CT for the differential diagnosis of solitary fibroma of pleura from other chest disease with low uptake of 18 F-FDG.

OBJECTIVE: We conducted a prospective study using 68 Ga-DOTA-FAPI-04 PET/computed tomography (CT) to differentiate solitary fibromas of pleura (SFP) from other chest similar masses showing low uptake of 18 F-FDG. METHODS: A prospective study including 13 patients was divided into two groups: five cases of SFP and eight of thoracic lesions resembling SFP on general imaging examination. Except for CT and MRI, all patients underwent both 18 F-FDG and 68 Ga-DOTA-FAPI-04 PET/CT examinations. Compare the differences of lesions in CT net enhancement value and the uptake of 18 F-FDG and 68 Ga-DOTA-FAPI-04 between the two groups. The values of CT and PET/CT for differential diagnosis were calculated by receiver operating characteristic (ROC) curves. RESULTS: The uptake of 68 Ga-DOTA-FAPI-04 in SFP was significantly higher than the others in chest, SUVmean (8.10 ± 5.57) versus (1.11 ± 0.38); and SUVmax (15.46 ± 8.16) versus (3.96 ± 2.43), and the difference was statistically significant ( P < 0.05). The 68 Ga-DOTA-FAPI-04 could effectively distinguish SFP from other lesions, and the accuracies of SUVmax and SUVmean for differential diagnosis were 92.31 and 100%, the corresponding cutoff value being 7.19 and 2.26. The uptake of 18 F-FDG in SFP was slightly lower than other lesions, SUVmean (1.63 ± 0.30) versus (1.88 ± 1.02); and SUVmax (2.51 ± 0.54) versus (3.60 ± 1.57), and the difference was not statistically significant ( P > 0.05). The SFP showed significant enhancement in the venous phase, but the difference was not statistically significant ( P > 0.05). CONCLUSION: The 68 Ga-DOTA-FAPI-04 has potential application value in differentiating SFP from lesions with low 18 F-FDG uptake, in addition, 68 Ga-DOTA-FAPI-04 may specifically target SFP.

Metabolomics Mechanism and Lignin Response to Laxogenin C, a Natural Regulator of Plants Growth.

Laxogenin C (LGC) is a natural spirostanol deriving from plant hormone which has shown growing regulation similar to those of brassinosteroids. In the present study, LGC showed a promoting effect on tomato seed germination and seedling growth in a dose-dependent manner. We applied LC-MS/MS to investigate metabolome variations in the tomato treated with LGC, which revealed 10 differential metabolites (DMs) related to KEGG metabolites, associated with low and high doses of LGC. Enrichment and pathway mapping based on the KEGG database indicated that LGC regulated expressions of 2-hydroxycinnamic acid and l-phenylalanine to interfere with phenylalanine metabolism and phenylpropanoids biosynthesis. The two pathways are closely related to plant growth and lignin formation. In our further phenotypic verification, LGC was confirmed to affect seedling lignification and related phenylpropanoids, trans-ferulic acid and l-phenylalanine levels. These findings provided a metabolomic aspect on the plant hormone derivates and revealed the affected metabolites. Elucidating their regulation mechanisms can contribute to the development of sustainable agriculture. Further studies on agrichemical development would provide eco-friendly and efficient regulators for plant growth control and quality improvement.

The role of PET molecular imaging in immune checkpoint inhibitor therapy in lung cancer: Precision medicine and visual monitoring.

Lung cancer is a malignant tumour originating from the bronchial epithelium or glands of the lung with high morbidity and mortality. For advanced lung cancer, the lack of effective treatment often results in poor prognosis. Immune checkpoint inhibitor (ICI) therapy, as a novel therapeutic method, upregulates immunity by blocking the negative regulation of tumours. In the clinical treatment process, not all lung cancer patients can benefit from ICI treatment. Therefore, screening patients who might potentially benefit from ICI therapy and evaluating the efficacy of ICIs has become an important part of therapy for lung cancer patients. This review has summarized the immune microenvironment of lung cancer, the mechanism of ICI therapy and its current application status. Importantly, we focused on the application of 18F-fluorodeoxyglucose (18F-FDG) and other targeted immune checkpoint tracers based on positron emission tomography (PET) for lung cancer, providing a reference for screening lung cancer candidates suitable for ICI therapy and evaluating the therapeutic effect. Finally, future research directions in PET molecular imaging and their potential application in ICI therapy for lung cancer are presented.

Giant cell tumour of the tendon sheath of the spine: clinical features and imaging findings.

OBJECTIVES: To review the clinical and imaging data of spinal giant cell tumour of the tendon sheath (GCTTS) to improve our understanding of the disease. METHODS: The imaging findings, clinicopathological features and clinical outcomes of 14 patients with pathologically confirmed spinal GCTTS were analysed retrospectively. RESULTS: All 14 patients had a single spinal lesion, including ten cervical vertebra lesions and four thoracic vertebra lesions. CT scan findings: The lesions showed osteolytic bone destruction and were centred on the facet joint, eroding the surrounding bone with a paravertebral soft tissue mass. MRI scan findings: all the lesions manifested predominantly as isointense or hypointense on T1-weighted imaging (T1WI). On T2-weighted imaging (T2WI), eight lesions were hypointense, and four were isointense. The remaining two lesions showed slight hyperintensity. The enhanced scans of eight lesions showed moderate to marked homogeneous or heterogeneous enhancement. PET/CT findings: Among the five patients who underwent PET/CT, three presented lesions with well-defined, sclerotic borders, and the uptake of 18F-FDG was markedly increased. One lesion showed an ill-defined border and an uneven increase in 18F-FDG uptake with an SUVmax value of 8.9. A recurrent lesion was only found on PET/CT 45 months after surgery and the SUVmax was 5.1. CONCLUSIONS: Spinal GCTTS is extremely rare. Osteolytic bone destruction in the area of the facet joint with a soft tissue mass and hypointensity on T2WI images are indicative of the spinal GCTTS. GCTTS shows high uptake of 18F-FDG, and PET/CT is helpful in detecting recurrent lesions.

Solitary Fibrous Tumors of the Pleura Shown on 18F-FDG and 68Ga-DOTA-FAPI-04 PET/CT.

ABSTRACT: A 52-year-old man complained of pain in the right lower chest wall for a month. Chest CT found a subpleural mass, but failed to identify the nature of the tumor. The 18F-FDG PET/CT was conducted for further diagnosis and staging, which showed the mass in the lower lobe of the right lung with mild radioactive uptake of 18F-FDG. The patient was subsequently enrolled in an ongoing clinical trial using 68Ga-DOTA-FAPI-04 (fibroblast activation protein inhibitor) PET/CT. The mass showed intensive 68Ga-DOTA-FAPI-04 uptake, which was subsequently confirmed as solitary fibrous tumors of the pleura by pathology. Our case demonstrated that the 68Ga-DOTA-FAPI-04 might have excellent tumor affinity of solitary fibrous tumors of the pleura.

Primary Extragastrointestinal Stromal Tumor on FDG PET/CT.

Primary extragastrointestinal stromal tumor is very rare. We report a case of cervical paravertebral extragastrointestinal stromal tumor involving adjacent bones revealed by FDG PET/CT in a 66-year-old man without any gastrointestinal involvement.