Summary
Cancer cells consume glucose and secrete lactate in culture. It is unknown whether lactate contributes to energy metabolism in living tumors. We previously reported that human non-small cell lung cancers (NSCLC) oxidize glucose in the tricarboxylic acid (TCA) cycle. Here we show that lactate is also a TCA cycle carbon source for NSCLC. In human NSCLC, evidence of lactate utilization was most apparent in tumors with high 18fluorodeoxyglucose uptake and aggressive oncological behavior. Infusing human NSCLC patients with 13C-lactate revealed extensive labeling of TCA cycle metabolites. In mice, deleting monocarboxylate transporter-1 (MCT1) from tumor cells eliminated lactate-dependent metabolite labeling, confirming tumor-cell autonomous lactate uptake. Strikingly, directly comparing lactate and glucose metabolism in vivo indicated that lactate's contribution to the TCA cycle predominates. The data indicate that tumors, including bona fide human NSCLC, can use lactate as a fuel in vivo.
Imaging plays an important role in the evaluation and management of acute pulmonary embolism (PE). Computed tomography (CT) pulmonary angiography (CTPA) is the current standard of care and provides accurate diagnosis with rapid turnaround time. CT also provides information on other potential causes of acute chest pain. With dual-energy CT, lung perfusion abnormalities can also be detected and quantified. Chest radiograph has limited utility, occasionally showing findings of PE or infarction, but is useful in evaluating other potential causes of chest pain. Ventilation-perfusion (VQ) scan demonstrates ventilation-perfusion mismatches in these patients, with several classification schemes, typically ranging from normal to high. Magnetic resonance imaging (MRI) also provides accurate diagnosis, but is available in only specialized centers and requires higher levels of expertise. Catheter pulmonary angiography is no longer used for diagnosis and is used only for interventional management. Echocardiography is used for risk stratification of these patients. In this article, we review the role of imaging in the evaluation of acute PE.
FDG PET/CT is a valuable imaging tool for assessing treatment response for patients with lung cancer, though evidence for its comparative effectiveness with chest CT is still evolving. FDG PET/CT is most useful when there is clinical suspicion or other evidence for disease recurrence or metastases. The sequencing, cost analysis, and comparative effectiveness of FDG PET/CT and conventional imaging modalities in the follow-up setting need to be investigated.
Background:In non-small cell lung cancer (NSCLC), fluorodeoxyglucose positron emission tomography (FDG-PET) assists in diagnosis, staging, and evaluating treatment response. One parameter of FDG-PET, the maximum standard uptake value (SUV m ), is considered an objective measure of glucose uptake. However, little is known about the fate of glucose in FDG-avid lung tumors in vivo. The objective is to use stable glucose isotope tracing to determine if the SUV m predicts glycolytic metabolism, or other glucose fates in tumors.
Methods:In this prospective IRB-approved clinical trial, 52 untreated potentially-resectable confirmed NSCLC patients underwent FDG-PET computed tomography. During surgery, the patients were infused with 13 C-glucose. Blood, tumor (T) and normal lung (NL) samples were analyzed by mass spectrometry to determine 13 C enrichment in glycolytic intermediates. These
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.