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BMC Research Notes Jun 2024The study objective was to investigate the potential of quantitative measures of pulmonary inflammation by [18 F]Fluorodeoxyglucose positron emission... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE AND RESULTS DESCRIPTION
The study objective was to investigate the potential of quantitative measures of pulmonary inflammation by [18 F]Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a surrogate marker of inflammation in COPD. Patients treated with anti-inflammatory Liraglutide were compared to placebo and correlated with inflammatory markers. 27 COPD-patients (14 receiving Liraglutide treatment and 13 receiving placebo) underwent 4D-respiratory-gated FDG-PET/CT before and after treatment. Two raters independently segmented the lungs from CT images and measured activity in whole lung, mean standard uptake values (SUVmean) corrected for lean-body-mass in the phase-matched PET images of the whole segmented lung volume, and total lesion glycolysis (TLG; SUVmean multiplied by volume). Inter-rater reliability was analyzed with Bland-Altman analysis and correlation plots. We found no differences in metabolic activity in the lungs between the two groups as a surrogate of pulmonary inflammation, and no changes in inflammation markers. The purpose of the research and brief summary of main findings. The degree of and changes in pulmonary inflammation in chronic obstructive pulmonary disease (COPD) may be difficult to ascertain. Measuring metabolic activity as a surrogate marker of inflammation by FDG-PET/CT may be useful, but data on its use in COPD including reproducibility is still limited, especially with respiration-gated technique, which should improve quantification in the lungs. We assessed several quantitative measures of metabolic activity and correlated them with inflammation markers, and we assessed reproducibility of the methods. We found no differences in metabolic activity between the two groups (before and after 40 weeks treatment with Liraglutide vs. placebo). Bland-Altman analysis showed good agreement between the two raters.
TRIAL REGISTRATION
The study was conducted between February 2018 and March 2020 at the Department of Pulmonary Diseases at Hospital South West Jutland and Lillebaelt Hospital, Denmark, and registered from March 2018 at clinicaltrials.gov with trial registration number NCT03466021.
Topics: Humans; Pulmonary Disease, Chronic Obstructive; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Male; Female; Aged; Middle Aged; Lung; Pneumonia; Liraglutide; Respiration; Radiopharmaceuticals
PubMed: 38902794
DOI: 10.1186/s13104-024-06820-w -
Oncotarget Jun 2024Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST... (Comparative Study)
Comparative Study
Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.
OBJECTIVES
Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [F]fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction.
RESULTS
imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST < 0.0001 and = 0.015, respectively; mRECIST < 0.0001 and = 0.015, respectively).
METHODS
Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2-4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods.
CONCLUSION
For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).
Topics: Humans; Ipilimumab; Male; Nivolumab; Female; Aged; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Middle Aged; Antineoplastic Combined Chemotherapy Protocols; Prognosis; Pleural Neoplasms; Mesothelioma, Malignant; Mesothelioma; Lung Neoplasms; Aged, 80 and over; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 38900646
DOI: 10.18632/oncotarget.28594 -
BioRxiv : the Preprint Server For... Jun 2024Heart failure involves metabolic alterations including increased glycolysis despite unchanged or decreased glucose oxidation. The mitochondrial pyruvate carrier (MPC)...
BACKGROUND
Heart failure involves metabolic alterations including increased glycolysis despite unchanged or decreased glucose oxidation. The mitochondrial pyruvate carrier (MPC) regulates pyruvate entry into the mitochondrial matrix, and cardiac deletion of the MPC in mice causes heart failure. How MPC deletion results in heart failure is unknown.
METHODS
We performed targeted metabolomics and isotope tracing in wildtype (fl/fl) and cardiac-specific Mpc2-/- (CS-Mpc2-/-) hearts after in vivo injection of U-C-glucose. Cardiac glycogen was assessed biochemically and by transmission electron microscopy. Cardiac uptake of 2-deoxyglucose was measured and western blotting performed to analyze insulin signaling and enzymatic regulators of glycogen synthesis and degradation. Isotope tracing and glycogen analysis was also performed in hearts from mice fed either low-fat diet or a ketogenic diet previously shown to reverse the CS-Mpc2-/- heart failure. Cardiac glycogen was also assessed in mice infused with angiotensin-II that were fed low-fat or ketogenic diet.
RESULTS
Failing CS-Mpc2-/- hearts contained normal levels of ATP and phosphocreatine, yet these hearts displayed increased enrichment from U-C-glucose and increased glycolytic metabolite pool sizes. C enrichment and pool size was also increased for the glycogen intermediate UDP-glucose, as well as increased enrichment of the glycogen pool. Glycogen levels were increased ~6-fold in the failing CS-Mpc2-/- hearts, and glycogen granules were easily detected by electron microscopy. This increased glycogen synthesis occurred despite enhanced inhibitory phosphorylation of glycogen synthase and reduced expression of glycogenin-1. In young, non-failing CS-Mpc2-/- hearts, increased glycolytic C enrichment occurred, but glycogen levels remained low and unchanged compared to fl/fl hearts. Feeding a ketogenic diet to CS-Mpc2-/- mice reversed the heart failure and normalized the cardiac glycogen and glycolytic metabolite accumulation. Cardiac glycogen levels were also elevated in mice infused with angiotensin-II, and both the cardiac hypertrophy and glycogen levels were improved by ketogenic diet.
CONCLUSIONS
Our results indicate that loss of MPC in the heart causes glycogen accumulation and heart failure, while a ketogenic diet can reverse both the glycogen accumulation and heart failure. We conclude that maintaining mitochondrial pyruvate import and metabolism is critical for the heart, unless cardiac pyruvate metabolism is reduced by consumption of a ketogenic diet.
PubMed: 38895296
DOI: 10.1101/2024.06.06.597841 -
CNS Neuroscience & Therapeutics Jun 2024The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering...
AIMS
The patient being minimally conscious state (MCS) may benefit from wake-up interventions aimed at improving quality of life and have a higher probability of recovering higher level of consciousness compared to patients with the unresponsive wakefulness syndrome (UWS). However, differentiation of the MCS and UWS poses challenge in clinical practice. This study aimed to explore glucose metabolic pattern (GMP) obtained from F-labeled-fluorodeoxyglucose positron emission tomography (F-FDG-PET) in distinguishing between UWS and MCS.
METHODS
Fifty-seven patients with disorders of consciousness (21 cases of UWS and 36 cases of MCS) who had undergone repeated standardized Coma Recovery Scale-Revised (CRS-R) evaluations were enrolled in this prospective study. F-FDG-PET was carried out in all patients and healthy controls (HCs). Voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was used to generate GMPs. The expression score of whole-brain GMP was obtained, and its diagnostic accuracy was compared with the standardized uptake value ratio (SUVR). The diagnostic efficiency was validated by one-year later clinical outcomes.
RESULTS
UWS-MCS GMP exhibited hypometabolism in the frontal-parietal cortex, along with hypermetabolism in the unilateral lentiform nucleus, putamen, and anterior cingulate gyrus. The UWS-MCS-GMP expression score was significantly higher in UWS compared to MCS patients (0.90 ± 0.85 vs. 0 ± 0.93, p < 0.001). UWS-MCS-GMP expression score achieved an area under the curve (AUC) of 0.77 to distinguish MCS from UWS, surpassing that of SUVR based on the frontoparietal cortex (AUC = 0.623). UWS-MCS-GMP expression score was significantly correlated with the CRS-R score (r = -0.45, p = 0.004) and accurately predicted the one-year outcome in 73.7% of patients.
CONCLUSION
UWS and MCS exhibit specific glucose metabolism patterns, the UWS-MCS-GMP expression score significantly distinguishes MCS from UWS, making SSM/PCA a potential diagnostic methods in clinical practice for individual patients.
Topics: Humans; Female; Male; Middle Aged; Adult; Glucose; Fluorodeoxyglucose F18; Brain; Positron-Emission Tomography; Persistent Vegetative State; Aged; Prospective Studies; Young Adult
PubMed: 38894559
DOI: 10.1111/cns.14787 -
Journal of Clinical Medicine May 2024: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented....
: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented. Thus, our research aimed to explore the potential impact of various TKIs of GLUT-1 on the standard [F]FDG-PET monitoring of tumor response in patients. : To achieve this, we conducted an analysis on three patients who were undergoing treatment with different TKIs and harbored actionable alterations. Alongside the assessment of FDG data (including SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV)), we also examined the changes in tumor sizes through follow-up [F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. : Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. : These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy.
PubMed: 38892979
DOI: 10.3390/jcm13113269 -
International Journal of Molecular... May 2024One aspect of ovarian tumorigenesis which is still poorly understood is the tumor-stroma interaction, which plays a major role in chemoresistance and tumor progression....
One aspect of ovarian tumorigenesis which is still poorly understood is the tumor-stroma interaction, which plays a major role in chemoresistance and tumor progression. Cancer-associated fibroblasts (CAFs), the most abundant stromal cell type in the tumor microenvironment, influence tumor growth, metabolism, metastasis, and response to therapy, making them attractive targets for anti-cancer treatment. Unraveling the mechanisms involved in CAFs activation and maintenance is therefore crucial for the improvement of therapy efficacy. Here, we report that CAFs phenoconversion relies on the glucose-dependent inhibition of autophagy. We show that ovarian cancer cell-conditioning medium induces a metabolic reprogramming towards the CAF-phenotype that requires the autophagy-dependent glycolytic shift. In fact, 2-deoxy-D-glucose (2DG) strongly hampers such phenoconversion and, most importantly, induces the phenoreversion of CAFs into quiescent fibroblasts. Moreover, pharmacological inhibition (by proline) or autophagy gene knockdown (by siBECN1 or siATG7) promotes, while autophagy induction (by either 2DG or rapamycin) counteracts, the metabolic rewiring induced by the ovarian cancer cell secretome. Notably, the nutraceutical resveratrol (RV), known to inhibit glucose metabolism and to induce autophagy, promotes the phenoreversion of CAFs into normal fibroblasts even in the presence of ovarian cancer cell-conditioning medium. Overall, our data support the view of testing autophagy inducers for targeting the tumor-promoting stroma as an adjuvant strategy to improve therapy success rates, especially for tumors with a highly desmoplastic stroma, like ovarian cancer.
Topics: Humans; Female; Autophagy; Cancer-Associated Fibroblasts; Ovarian Neoplasms; Glucose; Cell Line, Tumor; Tumor Microenvironment; Resveratrol; Culture Media, Conditioned; Deoxyglucose; Glycolysis
PubMed: 38891879
DOI: 10.3390/ijms25115691 -
BMC Pulmonary Medicine Jun 2024The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of...
BACKGROUND
The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare.
CASE PRESENTATION
A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant F-FDG uptake on F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis.
CONCLUSION
Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.
Topics: Humans; Female; Middle Aged; Thymoma; Lymphocytosis; Pleural Neoplasms; Bone Neoplasms; Positron Emission Tomography Computed Tomography; Thymus Neoplasms; T-Lymphocytes; Fluorodeoxyglucose F18; Diagnosis, Differential; Pleura
PubMed: 38877486
DOI: 10.1186/s12890-024-03090-x -
Science Advances Jun 2024In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity...
In vivo molecular imaging tools are crucially important for elucidating how cells move through complex biological systems; however, achieving single-cell sensitivity over the entire body remains challenging. Here, we report a highly sensitive and multiplexed approach for tracking upward of 20 single cells simultaneously in the same subject using positron emission tomography (PET). The method relies on a statistical tracking algorithm (PEPT-EM) to achieve a sensitivity of 4 becquerel per cell and a streamlined workflow to reliably label single cells with over 50 becquerel per cell of F-fluorodeoxyglucose (FDG). To demonstrate the potential of the method, we tracked the fate of more than 70 melanoma cells after intracardiac injection and found they primarily arrested in the small capillaries of the pulmonary, musculoskeletal, and digestive organ systems. This study bolsters the evolving potential of PET in offering unmatched insights into the earliest phases of cell trafficking in physiological and pathological processes and in cell-based therapies.
Topics: Positron Emission Tomography Computed Tomography; Animals; Single-Cell Analysis; Cell Tracking; Whole Body Imaging; Mice; Humans; Fluorodeoxyglucose F18; Cell Line, Tumor; Algorithms; Melanoma
PubMed: 38875333
DOI: 10.1126/sciadv.adk5747 -
Tuberkuloz Ve Toraks Jun 2024Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB...
Tuberculosis (TB) is an airborne infectious disease caused by Mycobacterium tuberculosis (MTB). Although it typically affects the lungs (pulmonary TB), one-fifth of TB cases present as extrapulmonary TB. The diagnosis of extrapulmonary TB is often overlooked due to its atypical clinical and radiological manifestations. Differentiating TB from neoplastic conditions poses significant challenges. A 33-year-old female patient was admitted to the emergency clinic with shortness of breath, cough, and abdominal pain. Postero-anterior chest X-ray revealed massive pleural effusion leading to mediastinal shift. With a preliminary diagnosis of malignant pleural effusion, a pleural catheter was inserted, and the patient was referred for a positron emission tomography (PET/CT) to assess the primary site and the optimal location for a biopsy. The PET/CT revealed asymmetric soft tissue thickening on the left side of the nasopharynx, and increased fluorodeoxyglucose (FDG) uptake in the left cervical lymph nodes raised suspicion regarding primary nasopharyngeal cancer. Additionally, there was an increased FDG uptake observed in the mass lesion located in the right upper lobe, mediastinal lymph nodes, pleural surfaces in the left hemithorax, perihepatic areas, and peritoneum, indicating diffuse metastatic disease. Tuberculosis diagnosis was confirmed through biopsies demonstrating granulomatous inflammation in the lung and nasopharynx, along with culturing MTB from pleural effusion. Positron emission tomography played a crucial role in identifying sites of TB involvement. Despite its rarity, healthcare professionals should consider nasopharyngeal TB as a potential diagnosis when evaluating nasopharyngeal masses.
Topics: Humans; Female; Adult; Diagnosis, Differential; Positron Emission Tomography Computed Tomography; Tuberculosis; Fluorodeoxyglucose F18; Neoplasm Metastasis
PubMed: 38869209
DOI: 10.5578/tt.202402915 -
Cancer Imaging : the Official... Jun 2024Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the...
BACKGROUND
Neuroblastoma (NB) is a highly heterogeneous tumor, and more than half of newly diagnosed NB are associated with extensive metastases. Accurately characterizing the heterogeneity of whole-body tumor lesions remains clinical challenge. This study aims to quantify whole-tumoral metabolic heterogeneity (WMH) derived from whole-body tumor lesions, and investigate the prognostic value of WMH in NB.
METHODS
We retrospectively enrolled 95 newly diagnosed pediatric NB patients in our department. Traditional semi-quantitative PET/CT parameters including the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean), the peak standardized uptake value (SUVpeak), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured. These PET/CT parameters were expressed as PSUVmax, PSUVmean, PSUVpeak, PMTV, PTLG for primary tumor, WSUVmax, WSUVmean, WSUVpeak, WMTV, WTLG for whole-body tumor lesions. The metabolic heterogeneity was quantified using the areas under the curve of the cumulative SUV-volume histogram index (AUC-CSH index). Intra-tumoral metabolic heterogeneity (IMH) and WMH were extracted from primary tumor and whole-body tumor lesions, respectively. The outcome endpoints were overall survival (OS) and progression-free survival (PFS). Survival analysis was performed utilizing the univariate and multivariate Cox proportional hazards regression. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic curve (ROC).
RESULTS
During follow up, 27 (28.4%) patients died, 21 (22.1%) patients relapsed and 47 (49.5%) patients remained progression-free survival, with a median follow-up of 35.0 months. In survival analysis, WMTV and WTLG were independent indicators of PFS, and WMH was an independent risk factor of PFS and OS. However, IMH only showed association with PFS and OS. In addition to metabolic parameters, the International Neuroblastoma Staging System (INSS) was identified as an independent risk factor for PFS, and neuron-specific enolase (NSE) served as an independent predictor of OS.
CONCLUSION
WMH was an independent risk factor for PFS and OS, suggesting its potential as a novel prognostic marker for newly diagnosed NB patients.
Topics: Humans; Neuroblastoma; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18; Male; Female; Retrospective Studies; Prognosis; Child, Preschool; Child; Infant; Radiopharmaceuticals; Adolescent; Tumor Burden
PubMed: 38863073
DOI: 10.1186/s40644-024-00718-3