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Journal of Nuclear Cardiology :... Dec 2023To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of...
BACKGROUND
To evaluate the feasibility of using radiolabeled fibroblast activation protein inhibitor (FAPI) PET/CT imaging to assess activated fibroblasts in the atria of individuals with AF and to identify factors contributing to enhanced atrial activity.
METHODS
We constructed left atrial appendage (LAA) pacing beagle dog AF models (n = 5) and conducted F-FAPI PET/CT imaging at baseline and eight weeks after pacing. Right atrial (RA) specimens were collected from these models. Additionally, 28 AF patients and ten age- and sex-matched healthy volunteers underwent F-FAPI PET/CT imaging.
RESULTS
RA of AF beagles showed increased F-FAPI uptake. Among AF patients, 18 out of 28 (64.3%) exhibited enhanced atrial FAPI activity. No atrial F-FAPI uptake was observed in the sham beagle and healthy volunteers. In animal RA specimens, F-FAPI activity correlated positively with FAP mRNA (r = .98, P = .002) and protein (r = .82, P = .03) levels, as well as collagen I mRNA expression (r = .85, P = .02). B-type natriuretic peptide levels were associated with atrial F-FAPI activity (OR = 3.01, P = .046).
CONCLUSION
This proof-of-concept study suggests that F-FAPI PET/CT imaging may be a feasible method for evaluating activated fibroblasts in the atria of AF patients.
Topics: Animals; Humans; Dogs; Atrial Fibrillation; Positron Emission Tomography Computed Tomography; Heart Atria; Fibroblasts; RNA, Messenger; Fluorodeoxyglucose F18
PubMed: 37626209
DOI: 10.1007/s12350-023-03352-x -
Scientific Reports May 2024Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study,...
Microglia are natural immune cells in the central nervous system, and the activation of microglia is accompanied by a reprogramming of glucose metabolism. In our study, we investigated the role of long non-coding RNA taurine-upregulated gene 1 (TUG1) in regulating microglial glucose metabolism reprogramming and activation. BV2 cells were treated with Lipopolysaccharides (LPS)/Interferon-γ (IFN-γ) to establish a microglial activation model. The glycolysis inhibitor 2-Deoxy-D-glucose (2-DG) was used as a control. The expression levels of TUG1 mRNA and proinflammatory cytokines such as Interleukin-1β (IL-1β), Interleukin -6, and Tumor Necrosis Factor-α mRNA and anti-inflammatory cytokines such as IL-4, Arginase 1(Arg1), CD206, and Ym1 were detected by RT-qPCR. TUG1 was silenced using TUG1 siRNA and knocked out using CRISPR/Cas9. The mRNA and protein expression levels of key enzymes involved in glucose metabolism, such as Hexokinase2, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Lactate dehydrogenase, Glucose 6 phosphate dehydrogenase, and Pyruvate dehydrogenase (PDH), were determined by RT-qPCR and Western blotting. The glycolytic rate of microglial cells was measured using Seahorse. Differential metabolites were determined by metabolomics, and pathway enrichment was performed using these differential metabolites. Our findings revealed that the expression of TUG1 was elevated in proinflammatory-activated microglia and positively correlated with the levels of inflammatory factors. The expression of anti-inflammatory cytokines such as IL-4, Arg1, CD206, and Ym1 were decreased when induced with LPS/IFN-γ. However, this decrease was reversed by the treatment with 2-DG. Silencing of GAPDH led to an increase in the expression of TUG1 and inflammatory factors. TUG1 knockout (TUG1KO) inhibited the expression of glycolytic key enzymes and promoted the expression of oxidative phosphorylation key enzymes, shifting the metabolic profile of activated microglia from glycolysis to oxidative phosphorylation. Additionally, TUG1KO reduced the accumulation of metabolites, facilitating the restoration of the tricarboxylic acid cycle and enhancing oxidative phosphorylation in microglia. Furthermore, the downregulation of TUG1 was found to reduce the expression of both proinflammatory and anti-inflammatory cytokines under normal conditions. Interestingly, when induced with LPS/IFN-γ, TUG1 downregulation showed a potentially beneficial effect on microglia in terms of inflammation. Downregulation of TUG1 expression inhibits glycolysis and facilitates the shift of microglial glucose metabolism from glycolysis to oxidative phosphorylation, promoting their transformation towards an anti-inflammatory phenotype and exerting anti-inflammatory effects in BV2.
Topics: Microglia; Animals; RNA, Long Noncoding; Glucose; Mice; Lipopolysaccharides; Glycolysis; Cytokines; Inflammation; Interferon-gamma; beta-N-Acetylhexosaminidases; Cell Line; Mannose Receptor; Mannose-Binding Lectins; Deoxyglucose; Interleukin-4; Interleukin-1beta; Metabolic Reprogramming; Arginase; Hexokinase; Lectins
PubMed: 38802677
DOI: 10.1038/s41598-024-62966-4 -
Expert Review of Cardiovascular Therapy 2024Infective endocarditis (IE) is an increasingly important condition with significant morbidity and mortality. With advancements in cardiovascular interventions including... (Review)
Review
INTRODUCTION
Infective endocarditis (IE) is an increasingly important condition with significant morbidity and mortality. With advancements in cardiovascular interventions including prosthetic valve implantation and utilization of intracardiac devices, the prevalence of IE is rising in the modern era. Early detection and management of this condition are critical.
AREAS COVERED
This review presents a contemporary review of the applications of multi-modality imaging in IE, taking a comparative approach of the various imaging modalities.
EXPERT OPINION
Transthoracic and transesophageal echocardiography are essential imaging modalities in establishing the diagnosis of IE, as well as evaluating for complications of IE. Other imaging modalities such as cardiac computed tomography and nuclear imaging play an important role as adjuvant imaging modalities for the evaluation of IE, particularly in prosthetic valve IE and cardiovascular implantable device associated IE. It is crucial to understand the strengths, weaknesses, and clinical application of each imaging modality, to improve the diagnosis, management, and outcomes of patients with IE.
Topics: Humans; Fluorodeoxyglucose F18; Endocarditis; Multimodal Imaging; Heart; Heart Valve Prosthesis; Endocarditis, Bacterial
PubMed: 37996246
DOI: 10.1080/14779072.2023.2288152 -
Molecular Imaging and Biology Dec 2023Gallium 68 (Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT is sensitive on breast cancer staging, but its clinical utility may be limited by the high...
PURPOSE
Gallium 68 (Ga)-labeled fibroblast activation protein inhibitor (FAPI) PET/CT is sensitive on breast cancer staging, but its clinical utility may be limited by the high physiological Ga-FAPI-04 uptake in normal breast tissue that can obscure primary tumors. The aim of this study was to elucidate the characteristics of physiological Ga-FAPI-04 uptake in normal breast.
PROCEDURES
A total of 143 consecutive women with Ga-FAPI-04 PET/CT data were reviewed retrospectively. SUV, density and thickness of breast, as well as SUV of nipple, were measured. Univariate and multivariate regression analyses were used to identify factors related to the breast and nipple SUVs.
RESULTS
Twenty-eight premenopausal, 62 menopausal and 10 post-operative (after bilateral adnexectomy) women with 103 examinations were included. All had a diffuse, symmetrical uptake in breast. There was no difference in Ga-FAPI-04 uptake between bilateral breasts (right: median, 1.14[IQR, 0.85-1.54] vs. left: median, 1.09[IQR, 0.86-1.54]; P = 0.253). Patients in menstrual status with expected high estrogen level (late follicular, ovulatory and mid luteal phases) had higher breast SUVs (median SUV, 3.91 [IQR, 2.85-4.35]) than those with expected moderate (early follicular, early luteal and late luteal phases; median SUV, 1.57 [IQR, 1.39-2.08]; P < 0.001) or low level (menopause and post-operation; median SUV, 0.98 [IQR, 0.83-1.21]; P < 0.001). Menstrual status was an independent predictors of breast SUV (r = 0.689, P < 0.001). All the patients had a focal, symmetrical uptake in nipples. Nipple SUV did not correlate with menstrual status (P = 0.913).
Topics: Humans; Female; Positron Emission Tomography Computed Tomography; Gallium Radioisotopes; Retrospective Studies; Breast; Fluorodeoxyglucose F18; Quinolines
PubMed: 37945972
DOI: 10.1007/s11307-023-01872-z -
Nuclear Medicine and Biology 2023Cell death is fundamental in health and disease and resisting cell death is a hallmark of cancer. Treatment of malignancy aims to cause cancer cell death, however... (Review)
Review
Cell death is fundamental in health and disease and resisting cell death is a hallmark of cancer. Treatment of malignancy aims to cause cancer cell death, however current clinical imaging of treatment response does not specifically image cancer cell death but assesses this indirectly either by changes in tumor size (using x-ray computed tomography) or metabolic activity (using 2-[F]fluoro-2-deoxy-glucose positron emission tomography). The ability to directly image tumor cell death soon after commencement of therapy would enable personalised response adapted approaches to cancer treatment that is presently not possible with current imaging, which is in many circumstances neither sufficiently accurate nor timely. Several cell death pathways have now been identified and characterised that present multiple potential targets for imaging cell death including externalisation of phosphatidylserine and phosphatidylethanolamine, caspase activation and La autoantigen redistribution. However, targeting one specific cell death pathway carries the risk of not detecting cell death by other pathways and it is now understood that cancer treatment induces cell death by different and sometimes multiple pathways. An alternative approach is targeting the cell death phenotype that is "agnostic" of the death pathway. Cell death phenotypes that have been targeted for cell death imaging include loss of plasma membrane integrity and dissipation of the mitochondrial membrane potential. Targeting the cell death phenotype may have the advantage of being a more sensitive and generalisable approach to cancer cell death imaging. This review describes and summarises the approaches and radiopharmaceuticals investigated for imaging cell death by targeting cell death pathways or cell death phenotype.
Topics: Humans; Fluorodeoxyglucose F18; Neoplasms; Positron-Emission Tomography; Tomography, X-Ray Computed; Radiopharmaceuticals
PubMed: 37598518
DOI: 10.1016/j.nucmedbio.2023.108380 -
Journal of Nuclear Medicine : Official... Dec 2023Nonspecific lymph node uptake on F-FDG PET/CT imaging is a significant pitfall for tumor staging. Fibroblast activation protein α expression on cancer-associated... (Observational Study)
Observational Study
Nonspecific lymph node uptake on F-FDG PET/CT imaging is a significant pitfall for tumor staging. Fibroblast activation protein α expression on cancer-associated fibroblasts and some tumor cells is less sensitive to acute inflammatory stimuli, and fibroblast activation protein-directed PET may overcome this limitation. Eighteen patients from our prospective observational study underwent F-FDG and Ga fibroblast activation protein inhibitor (FAPI) PET/CT scans within a median of 2 d (range, 0-22 d). Lymph nodes were assessed on histopathology and compared with SUV measurements. On a per-patient basis, lymph nodes were rated malignant in 10 (56%) versus 7 (39%) patients by F-FDG PET/CT versus Ga-FAPI PET/CT scans, respectively, with a respective accuracy of 55% versus 94% for true lymph node metastases. Five of 6 (83%) false-positive nodes on the F-FDG PET/CT scans were rated true negative by the Ga-FAPI PET/CT scans. On a per-lesion basis, tumor detection rates were similar (85/89 lesions, 96%). Ga-FAPI PET/CT imaging demonstrated higher accuracy for true nodal involvement and therefore has the potential to replace F-FDG PET/CT imaging for cancer staging.
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Gallium Radioisotopes; Positron-Emission Tomography; Lymph Nodes; Quinolines
PubMed: 37734836
DOI: 10.2967/jnumed.123.265751 -
Journal of Nuclear Medicine : Official... Oct 2023This study aimed to develop an analytic approach based on [F]FDG PET radiomics using stacking ensemble learning to improve the outcome prediction in diffuse large B-cell...
This study aimed to develop an analytic approach based on [F]FDG PET radiomics using stacking ensemble learning to improve the outcome prediction in diffuse large B-cell lymphoma (DLBCL). In total, 240 DLBCL patients from 2 medical centers were divided into the training set ( = 141), internal testing set ( = 61), and external testing set ( = 38). Radiomics features were extracted from pretreatment [F]FDG PET scans at the patient level using 4 semiautomatic segmentation methods (SUV threshold of 2.5, SUV threshold of 4.0 [SUV4.0], 41% of SUV, and SUV threshold of mean liver uptake [PERCIST]). All extracted features were harmonized with the ComBat method. The intraclass correlation coefficient was used to evaluate the reliability of radiomics features extracted by different segmentation methods. Features from the most reliable segmentation method were selected by Pearson correlation coefficient analysis and the LASSO (least absolute shrinkage and selection operator) algorithm. A stacking ensemble learning approach was applied to build radiomics-only and combined clinical-radiomics models for prediction of 2-y progression-free survival and overall survival based on 4 machine learning classifiers (support vector machine, random forests, gradient boosting decision tree, and adaptive boosting). Confusion matrix, receiver-operating-characteristic curve analysis, and survival analysis were used to evaluate the model performance. Among 4 semiautomatic segmentation methods, SUV4.0 segmentation yielded the highest interobserver reliability, with 830 (66.7%) selected radiomics features. The combined model constructed by the stacking method achieved the best discrimination performance. For progression-free survival prediction in the external testing set, the areas under the receiver-operating-characteristic curve and accuracy of the stacking-based combined model were 0.771 and 0.789, respectively. For overall survival prediction, the stacking-based combined model achieved an area under the curve of 0.725 and an accuracy of 0.763 in the external testing set. The combined model also demonstrated a more distinct risk stratification than the International Prognostic Index in all sets (log-rank test, all < 0.05). The combined model that incorporates [F]FDG PET radiomics and clinical characteristics based on stacking ensemble learning could enable improved risk stratification in DLBCL.
Topics: Humans; Fluorodeoxyglucose F18; Reproducibility of Results; Lymphoma, Large B-Cell, Diffuse; Prognosis; Machine Learning
PubMed: 37500261
DOI: 10.2967/jnumed.122.265244 -
Cancer Medicine Aug 2023Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of predictive and prognostic models for outcome prediction using positron emission tomography radiomics in head and neck squamous cell carcinoma patients.
BACKGROUND
Positron emission tomography (PET) images of head and neck squamous cell carcinoma (HNSCC) patients can assess the functional and biochemical processes at cellular levels. Therefore, PET radiomics-based prediction and prognostic models have the potentials to understand tumour heterogeneity and assist clinicians with diagnosis, prognosis and management of the disease. We conducted a systematic review of published modelling information to evaluate the usefulness of PET radiomics in the prediction and prognosis of HNSCC patients.
METHODS
We searched bibliographic databases (MEDLINE, Embase, Web of Science) from 2010 to 2021 and considered 31 studies with pre-defined inclusion criteria. We followed the CHARMS checklist for data extraction and performed quality assessment using the PROBAST tool. We conducted a meta-analysis to estimate the accuracy of the prediction and prognostic models using the diagnostic odds ratio (DOR) and average C-statistic, respectively.
RESULTS
Manual segmentation method followed by 40% of the maximum standardised uptake value (SUV ) thresholding is a commonly used approach. The area under the receiver operating curves of externally validated prediction models ranged between 0.60-0.87, 0.65-0.86 and 0.62-0.75 for overall survival, distant metastasis and recurrence, respectively. Most studies highlighted an overall high risk of bias (outcome definition, statistical methodologies and external validation of models) and high unclear concern in terms of applicability. The meta-analysis showed the estimated pooled DOR of 6.75 (95% CI: 4.45, 10.23) for prediction models and the C-statistic of 0.71 (95% CI: 0.67, 0.74) for prognostic models.
CONCLUSIONS
Both prediction and prognostic models using clinical variables and PET radiomics demonstrated reliable accuracy for detecting adverse outcomes in HNSCC, suggesting the prospect of PET radiomics in clinical settings for diagnosis, prognosis and management of HNSCC patients. Future studies of prediction and prognostic models should emphasise the quality of reporting, external model validation, generalisability to real clinical scenarios and enhanced reproducibility of results.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Prognosis; Reproducibility of Results; Positron-Emission Tomography; Head and Neck Neoplasms; Fluorodeoxyglucose F18
PubMed: 37353996
DOI: 10.1002/cam4.6278 -
Anticancer Research Sep 2023F-fluorodeoxyglucose (FDG) is known to accumulate in the liver. We investigated whether accumulation of FDG was correlated with the degree of liver fibrosis and the...
BACKGROUND/AIM
F-fluorodeoxyglucose (FDG) is known to accumulate in the liver. We investigated whether accumulation of FDG was correlated with the degree of liver fibrosis and the grade of necro-inflammatory activity.
PATIENTS AND METHODS
This retrospective study included 35 patients who underwent FDG-positron emission tomography (PET)/computed tomography (CT) before liver surgery. On fusion images of CT and PET, by placing regions of interest on the lateral, anterior and posterior segments of the liver and the aorta, the standardized uptake value (SUV) mean, and SUV normalized by lean body mass (SUL) mean of the liver were measured, and the ratio SUVmean liver/SUVmean aorta was calculated. According to the New Inuyama Classification, subjects were classified into three groups based on the grade of liver-fibrosis degree, i.e., F0, F1+F2 and F3+F4, and into three groups based on the grade of necro-inflammatory activity, i.e., A0, A1 and A2. Each of the above parameters was then compared among the groups using a Tukey test.
RESULTS
Average SULmean liver values of the F0, F1+F2 and F3+F4 groups were 1.573±0.211, 1.845±0.220 and 1.716±0.119, respectively. The SULmean liver of the F1+F2 group was significantly higher than that of the F0 group (p=0.0296). No significant difference was observed for the other two parameters. None of the parameters exhibited significant difference among the A0, A1, and A2 groups.
CONCLUSION
FDG accumulation in the liver may be increased in the early stage of liver fibrosis. SULmean liver could be used to determine the necessity for therapeutic intervention in chronic liver disease.
Topics: Humans; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Retrospective Studies; Liver Cirrhosis
PubMed: 37648319
DOI: 10.21873/anticanres.16614 -
Cardiovascular Research Aug 2023
Topics: Humans; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Diabetes Mellitus, Type 1; Positron-Emission Tomography; Inflammation
PubMed: 37463514
DOI: 10.1093/cvr/cvad109