Background-The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD. Methods and Results-A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74;

Tumor chemoresistance is associated with high aerobic glycolysis rates and reduced oxidative phosphorylation, a phenomenon called “Warburg effect” whose reversal could impair the ability of a wide range of cancer cells to survive in the presence or absence of chemotherapy. In previous studies, Short-term-starvation (STS) was shown to protect normal cells and organs but to sensitize different cancer cell types to chemotherapy but the mechanisms responsible for these effects are poorly understood. We tested the cytotoxicity of Oxaliplatin (OXP) combined with a 48hour STS on the progression of CT26 colorectal tumors. STS potentiated the effects of OXP on the suppression of colon carcinoma growth and glucose uptake in both in vitro and in vivo models. In CT26 cells, STS down-regulated aerobic glycolysis, and glutaminolysis, while increasing oxidative phosphorylation. The STS-dependent increase in both Complex I and Complex II-dependent O2 consumption was associated with increased oxidative stress and reduced ATP synthesis. Chemotherapy caused additional toxicity, which was associated with increased succinate/Complex II-dependent O2 consumption, elevated oxidative stress and apoptosis.These findings indicate that the glucose and amino acid deficiency conditions imposed by STS promote an anti-Warburg effect characterized by increased oxygen consumption but failure to generate ATP, resulting in oxidative damage and apoptosis.

Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of 18F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the “in vivo” relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer.

Positron emission tomography (PET) combined with computed tomography (CT) is an established diagnostic modality that has become an essential imaging tool in oncological practice. However, thanks to its noninvasive nature and its capability to provide physiological information, the main applications of this technique have significantly expanded. 18F-labelled fluorodeoxyglucose (FDG) is the most commonly used radiopharmaceutical for PET scanning and demonstrates metabolic activity in various tissues. Since activated inflammatory cells, like malignant cells, predominantly metabolise glucose as a source of energy and increase expression of glucose transporters when activated, FDG-PET/CT can be successfully used to detect and monitor a variety of lung diseases, such as infections and several inflammatory conditions.The added value of FDG-PET/CT as a molecular imaging technique relies on its capability to identify disease in very early stages, long before the appearance of structural changes detectable by conventional imaging. Furthermore, by detecting the active phase of infectious or inflammatory processes, disease progression and treatment efficacy can be monitored. This review will focus on the clinical use of FDG-PET/CT in nonmalignant pulmonary diseases. @ERSpublications PET/CT is an imaging modality that could play a role in evaluation of inflammatory and infectious lung diseases

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In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects.

The favourable kinetics of 18 F-fluoro-2-deoxyglucose (FDG) permits to depict cancer glucose consumption by a single evaluation of late tracer uptake. This standard procedure relies on the slow radioactivity loss, usually attributed to the limited tumour expression of G6P-phosphatase (G6Pase). However, this classical interpretation intrinsically represents an approximation since, as in all tissues, cancer G6Pase activity is remarkable and is confined to the endoplasmic reticulum (ER), whose lumen must be reached by phosphorylated FDG to explain its hydrolysis and radioactivity release. The present study tested the impact of G6Pase sequestration on the mathematical description of FDG trafficking and handling in cultured cancer cells. Our data show that accounting for tracer access to the ER configures this compartment as the preferential site of FDG accumulation. This is confirmed by the reticular localization of fluorescent FDG analogues. Remarkably enough, reticular accumulation rate of FDG is dependent upon extracellular glucose availability, thus configuring the same ER as a significant determinant of cancer glucose metabolism.