1. What are the contributions in "Brain tumor imaging" ?
This brief review considers the role of magnetic resonance imaging and spectroscopy, and positron emission tomography in these areas and discusses the factors that limit translation of new techniques to the clinic, in particular, the cost and difficulties associated with validation in multicenter clinical trials.
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![Fig 1. Schematic illustration of metabolic pathways observable using hyperpolarized 13Clabeled probes. [U-2H, U-13C]glucosemeasures flux in glycolysis and the pentose phosphate pathway (PPP). [1-13C] pyruvate exchanges the hyperpolarized 13C label with the endogenous lactate and alanine pools and is converted irreversibly into CO2, which is in a rapid equilibrium with bicarbonate. The label in [2-13C] pyruvate is incorporated into acetyl-coenzyme A and allows assessment of flux in the tricarboxylic acid cycle. [5-13C]glutamine can be used to monitor glutaminolysis and [1-13C] glutamate exchanges the hyperpolarized 13C label with a-ketoglutarate. [1-13C]a-ketoglutarate can be used to probe reversible conversion to glutamate and to 2-hydroxyglutarate. For clarity, some intermediate metabolic steps are not shown. ALT, alanine transaminase; AST, aspartate transaminase; BCAT, branched chain amino acid transaminase; CA, carbonic anhydrase; GLDH, glutamate dehydrogenase; GLS, glutaminase; GS, glutamine synthetase; IDH1, isocitrate dehydrogenase 1; LDH, lactate dehydrogenase; OAA, oxaloacetate; PC, pyruvate carboxylase; PDH, pyruvate dehydrogenase.](/figures/fig-1-schematic-illustration-of-metabolic-pathways-29quh886.png)
![Fig 3. Positron emission tomography images and cellular uptake mechanisms for nine clinical radiotracers for brain tumor imaging. ACE, [11C]acetate; ACSS, acetylcoenzyme A synthetase; ASCT2, neutral amino acid transporter, SLC1A5; FACBC, trans-1-amino-3-[18F]-fluorocyclobutane-carboxylic acid; FAS, fatty acid synthase; FDOPA, [18F]fluorodihydroxyphenylalanine; FET, [18F]fluoroethyltyrosine; FGln, 4-18F-(2S,4R)-fluoroglutamine; FLT, 39-deoxy-39[18F]-fluorothymidine; FMISO, [18F]fluoromisonidazole; FSPG, (4S)-4-(3-[18F]fluoropropyl)-L-glutamate; hENT, human equilibrative nucleoside transporter, SLC29A1; LAT1/2, large neutral amino acids transporters, SLC7A5 and SLC7A8; MCT, monocarboxylate transporter, SLC16A1; MET, [11C]methionine; pO2, partial pressure of oxygen; ROS, reactive oxygen species; TK1, thymidine kinase 1; XC 2, cystine/glutamate transporter, SLC7A11. Images reprinted with permission from Venneti et al,68 Mittra et al,69 Bruehlmeier et al,70 Kondo et al,71 Yamamoto et al,72 Toyota et al,73 and Juhasz et al.74](/figures/fig-3-positron-emission-tomography-images-and-cellular-373wndrs.png)
![Fig 2. Representative images of (C) hyperpolarized [1-13C]pyruvate and (D) [1-13C]lactate in a C6 glioma-bearing animal before (top) and 96 hours after radiotherapy (bottom). The metabolic images are shown in false color, overlaid on the 1H image of tissue anatomy. (A) A chemical shift image data set and (B) a contrast agent enhanced proton image are shown. The tumor is visible as a contrast agent– enhancing region at the top of the brain. (D) The [1-13C]lactate signal from the tumor was reduced after exposure to 15 Gy radiation. Reprinted with permission from Day et al.63](/figures/fig-2-representative-images-of-c-hyperpolarized-1-13c-2y3wpvjg.png)