Contribution of microarrays of gene expression (MAGE) to the definition of PET/CT as a qualified biomarker of early response in metastatic patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11573-11573
Author(s):  
Manuel Sureda ◽  
Aurora Crespo-Jara ◽  
Ramon Gonzalez Manzano ◽  
Maria del Carmen Redal ◽  
Francisco Javier Garcia-Cases ◽  
...  

11573 Background: Proliferating cancer cells consume elevated quantity of glucose, converted into lactate regardless the presence of oxygen (Warburg effect). This effect has been useful for imaging metabolically active tumors with FDG-PET, although its use in early response is controversial. Molecular mechanisms of FDG uptake are not fully understood. We have used MAGE to determine the most relevant genes involved in FDG uptake. Methods: Fresh-frozen tumor biopsies and quantitative basal FDG-PET/CT were obtained from metastatic lesions in cancer patients. Total tumor RNA was hybridized to a whole human genome oligonucleotide microarray. Gene expression signature-based prediction, using the most relevant genes involved in FDG uptake measured by SUV, was finally determined by Partial Least Squares (PLS). The interpretation of biological phenomena (IBP) derived from the selected genes was made by means of different public statistical bioinformatics resources. Results: 71 patients with different histological diagnosis were included in the training cohort and 13 in the validation one. 909 probes correlated significantly with SUV: 333 positively and 576 negatively. A predictive signature based on these 909 probes was built using PLS-3, with an RMSE in the validation set of 0.645 (within the 95% CI of RMSE determined in the training set). In IBP, other biological processes were more relevant than glycolysis in FDG uptake: RNA processing, ribosome biogenesis, protein processing, cell adhesion, cytoskeleton organization, angiogenesis and autophagy. Conclusions: This PLS-3-built signature is the first reported one that can accurately predict SUV. FDG uptake is a complex phenomenon that involves multiple biological processes, confirming the value of PET/CT in early response.

2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Malik ◽  
M Yazdani ◽  
SM Gould ◽  
E Reyes

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial inflammation may occur in the context of a multisystem disease such as sarcoidosis, adversely affecting prognosis. A definitive diagnosis of cardiac sarcoidosis (CS) is essential to implementing life-saving treatment but this is complicated by the invasive nature of endomyocardial biopsy (EMB) and its low accuracy. Positron emission tomography (PET) assists in diagnosis, which relies on visual interpretation of myocardial F-18 FDG uptake. The value of quantitative analysis and its application to clinical practice remain uncertain. Purpose To investigate the power of quantitative F-18 FDG PET-CT imaging analysis for detecting CS in patients with suspected disease. Methods All patients underwent F-18 FDG PET-CT after a 24-hour low-carbohydrate diet and 15-hour fasting as part of their diagnostic work-up for suspected cardiac inflammation. Cardiovascular magnetic resonance acted as gatekeeper to PET-CT in 8 of every 10 scans. Myocardial F-18 FDG uptake was assessed qualitatively and quantitatively using both manually drawn regions of interest and automatic polar maps to measure global and segmental standardised F-18 FDG uptake values (SUV).  The coefficient of variation (CoV) was calculated to determine uptake heterogeneity. To confirm diagnosis, follow-up data regarding disease progression, further testing and treatment were collected. To allow for sufficient follow-up time, the first 40 consecutive patients from a prospective registry (n= 214; Sep 2017-Jun 2020) were included. Results A comprehensive clinical picture was obtained successfully in 37 patients (median [IQR], 17 [13.5] months) and a final diagnosis of CS reached in 7 (disease prevalence, 19%). EMB was performed in 2 patients only while 3 underwent PPM/ICD implantation. Significant predictors of CS were fulfilment of Japanese Ministry of Health and Welfare criteria (Wald, 6.44; p = 0.01) and left ventricular dysfunction (Wald 6.72; p = 0.01). Qualitative F-18 FDG PET-CT had a high negative (95%) but low positive (45%) predictive value for CS (sensitivity, 83%; specificity, 77%). F-18 FDG SUV CoV was the strongest imaging predictor (Wald, 6.77; p = 0.009) and was significantly higher in CS than non-CS (CoV median [quartiles], 0.26 [0.21, 0.36] and 0.12 [0.11, 0.14] respectively; p = 0.004). As per ROC curve analysis (AUC, 0.84), a CoV threshold of 0.20 was highly specific (93%) and sensitive (86%) for CS. Conclusion In a referring population with a low prevalence of cardiac sarcoidosis, F-18 FDG PET-CT imaging is sensitive for the detection of myocardial inflammation with active disease unlikely in patients with a negative scan. Quantitative evaluation of metabolic heterogeneity within the myocardium provides a strong, independent marker of active disease and should be considered alongside visual assessment.


2020 ◽  
Vol 50 (1) ◽  
pp. 249-254
Author(s):  
Miho Sasaki ◽  
Yuka Hotokezaka ◽  
Reiko Ideguchi ◽  
Masataka Uetani ◽  
Shuichi Fujita

AbstractMyositis ossificans (MO) is a benign soft-tissue lesion characterized by the heterotopic formation of the bone in skeletal muscles, usually due to trauma. MO is occasionally difficult to diagnose because of its clinical and radiological similarities with malignancy. We report a case of traumatic MO (TMO) in the masseter and brachial muscles of a 37-year-old man who presented with painless swelling in the left cheek and severe trismus. Due to the absence of a traumatic history at the first consultation and identification of a tumorous lesion in the left masseter muscle by magnetic resonance imaging (MRI), the lesion was suspected to be a malignant tumor. Subsequently, 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) showed multiple regions of high FDG uptake across the whole body, suggestive of multiple metastases or other systemic diseases. However, intramuscular calcifications were also observed in the left masseter and brachial muscles, overlapping the areas with high FDG uptake. Moreover, multiple fractures were seen in the rib and lumbar spine, also overlapping the areas with high FDG uptake. Based on these imaging findings, along with a history of jet-ski trauma, TMO was suspected. The left cheek mass was surgically excised and histologically diagnosed as TMO. In this case report, FDG-PET/CT could detect multiple TMOs across the whole body. To the best of our knowledge, cases of multiple TMOs located far apart in different muscles are rare, and this may be the first report.


Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 839
Author(s):  
Tzu-Chuan Ho ◽  
Chin-Chuan Chang ◽  
Hung-Pin Chan ◽  
Ying-Fong Huang ◽  
Yi-Ming Arthur Chen ◽  
...  

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: “asymptomatic”, “COVID-19”, “[18F]FDG PET/CT”, and “nuclear medicine” were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.


CHEST Journal ◽  
2015 ◽  
Vol 148 (4) ◽  
pp. 168A
Author(s):  
MYUNGSUN LEE ◽  
Ina Jung ◽  
Youngran Kim ◽  
Jiyeon Lee

2017 ◽  
Vol 91 (21) ◽  
Author(s):  
Julie Dyall ◽  
Reed F. Johnson ◽  
Svetlana Chefer ◽  
Christopher Leyson ◽  
David Thomasson ◽  
...  

ABSTRACT Real-time bioimaging of infectious disease processes may aid countermeasure development and lead to an improved understanding of pathogenesis. However, few studies have identified biomarkers for monitoring infections using in vivo imaging. Previously, we demonstrated that positron emission tomography/computed tomography (PET/CT) imaging with [18F]-fluorodeoxyglucose (FDG) can monitor monkeypox disease progression in vivo in nonhuman primates (NHPs). In this study, we investigated [18F]-FDG-PET/CT imaging of immune processes in lymphoid tissues to identify patterns of inflammation in the monkepox NHP model and to determine the value of [18F]-FDG-PET/CT as a biomarker for disease and treatment outcomes. Quantitative analysis of [18F]-FDG-PET/CT images revealed differences between moribund and surviving animals at two sites vital to the immune response to viral infections, bone marrow and lymph nodes (LNs). Moribund NHPs demonstrated increased [18F]-FDG uptake in bone marrow 4 days postinfection compared to surviving NHPs. In surviving, treated NHPs, increase in LN volume correlated with [18F]-FDG uptake and peaked 10 days postinfection, while minimal lymphadenopathy and higher glycolytic activity were observed in moribund NHPs early in infection. Imaging data were supported by standard virology, pathology, and immunology findings. Even with the limited number of subjects, imaging was able to differentiate the difference between disease outcomes, warranting additional studies to demonstrate whether [18F]-FDG-PET/CT can identify other, subtler effects. Visualizing altered metabolic activity at sites involved in the immune response by [18F]-FDG-PET/CT imaging is a powerful tool for identifying key disease-specific time points and locations that are most relevant for pathogenesis and treatment. IMPORTANCE Positron emission tomography and computed tomography (PET/CT) imaging is a universal tool in oncology and neuroscience. The application of this technology to infectious diseases is far less developed. We used PET/CT imaging with [18F]-labeled fluorodeoxyglucose ([18F]-FDG) in monkeys after monkeypox virus exposure to monitor the immune response in lymphoid tissues. In lymph nodes of surviving monkeys, changes in [18F]-FDG uptake positively correlated with enlargement of the lymph nodes and peaked on day 10 postinfection. In contrast, the bone marrow and lymph nodes of nonsurvivors showed increased [18F]-FDG uptake by day 4 postinfection with minimal lymph node enlargement, indicating that elevated cell metabolic activity early after infection is predictive of disease outcome. [18F]-FDG-PET/CT imaging can provide real-time snapshots of metabolic activity changes in response to viral infections and identify key time points and locations most relevant for monitoring the development of pathogenesis and for potential treatment to be effective.


2013 ◽  
Vol 39 (12) ◽  
pp. 1358-1363 ◽  
Author(s):  
W.P. Andrade ◽  
E.N.P. Lima ◽  
C.A.B.T. Osório ◽  
M. do Socorro Maciel ◽  
G. Baiocchi ◽  
...  

2020 ◽  
Author(s):  
Connor Rogerson ◽  
Samuel Ogden ◽  
Edward Britton ◽  
Yeng Ang ◽  
Andrew D. Sharrocks ◽  
...  

AbstractOesophageal adenocarcinoma (OAC) is one of the most common causes of cancer deaths and yet compared to other common cancers, we know relatively little about the underlying molecular mechanisms. Barrett’s oesophagus (BO) is the only known precancerous precursor to OAC, but our understanding about the specific events leading to OAC development is limited. Here, we have integrated gene expression and chromatin accessibility profiles of human biopsies of BO and OAC and identified a strong cell cycle gene expression signature in OAC compared to BO. Through analysing associated chromatin accessibility changes, we have implicated the transcription factor KLF5 in the transition from BO to OAC. Importantly, we show that KLF5 expression is unchanged during this transition, but instead, KLF5 is redistributed across chromatin in OAC cells to directly regulate cell cycle genes specifically in OAC. Our findings have potential prognostic significance as the survival of patients with high expression of KLF5 target genes is significantly lower. We have provided new insights into the gene expression networks in OAC and the mechanisms behind progression to OAC, chiefly the repurposing of KLF5 for novel regulatory activity in OAC.


2012 ◽  
Vol 167 (9) ◽  
pp. 712-718
Author(s):  
H. H. Park ◽  
M. S. Park ◽  
C. H. Lee ◽  
J. H. Cho ◽  
K. R. Dong ◽  
...  
Keyword(s):  
Fdg Pet ◽  
Pet Ct ◽  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Fabio Chirillo ◽  
Franco Boccaletto ◽  
Paola Pantano ◽  
Alessandro De Leo ◽  
Marta Possamai ◽  
...  

The diagnosis of infective endocarditis (IE) is sometimes difficult when there are discrepancies between blood cultures, transesophageal echocardiography (TEE) and clinical judgment. The aim of this study was to assess the incremental diagnostic value of 18 F-FDG-PET/CT in 45 consecutive patients (73% male, mean age 61 ± 26 years) with suspected IE and inconclusive tests at admission. In 28 patients (19 with a cardiac valvular (15) or nonvalvular (4) device) with blood cultures positive for germs typically involved in IE the initial TEE was negative or inconclusive. In 10 patients presenting with fever TEE identified cardiac lesion possibly related to IE (ruptured mitral chordae, thickened valve leaflet, thickened prosthetic annulus), but blood cultures were persistently negative. Finally, 7 patients had metastatic or embolic lesions and a predisposing cardiac condition, but TEE was negative. When previous unknown lesions detected by PET/CT were confirmed by succeeding examinations, they were considered true positives. When PET/CT was negative, it was compared with the final diagnosis that was defined according to the modified Duke criteria determined during a 6-month follow-up. Thirty patients had definite IE at the end of the follow-up, 3 had possible IE, and in 12 patients the diagnosis was rejected. Twenty-seven patients (60%) exhibited abnormal FDG uptake around the cardiac valves, and 12 (27%) had extracardiac accumulation. In 5 patients the initial negative TEE became positive a mean 5 ±7 days after PET/CT had been performed The sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT were as follows (95% confidence interval): 87% (68% to 95%), 67% (38% to 87%), 84% (65% to 94%), and 71% (42% to 92%), respectively. Adding abnormal FDG uptake as a new major criterion significantly increased the sensitivity of the modified Duke criteria at admission (68% [53% to 82%] vs. 96% [88% to 99%], p = 0.01). This result was due to a significant reduction (p < 0.001) in the number of possible IE cases. In conclusion PET/CT increases the diagnostic accuracy for IE in the subset of patients with possible IE and may help to manage a challenging situation.


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