E into mice, both acetyl CoA and acetyl carnitine were observed in liver and heart,

E into mice, both acetyl CoA and acetyl carnitine were observed in liver and heart, although the acetyl carnitine signal from the heart PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/2073038 was higher, demonstrating an organ variation in the distribution of acetate metabolism [142]. Ischemia in skeletal muscle was shown to result in a reduction in acetyl-carnitine formation [142]. Carnitine can modulate fatty acid and carbohydrate metabolism by modifying the intramitochondrial acetyl-CoA/CoA ratio, and therefore, it is possible that this substrate could be used to probe fatty acid metabolism.[1-13C]lactate[1- C]Lactate has been hyperpolarized and investigated as an in vivo metabolic imaging agent [140]. After intravenous injection in the TRAMP model, only low levels of hyperpolarized [1-13C]pyruvate were detected, and this presumably reflects the exchange of label into a relatively small pool of tissue pyruvate. The hyperpolarized 13C label was also diluted by flux into other metabolites, including [1-13C]alanine and H13CO3-. An important advantage of using lactate to introduce the hyperpolarized 13C label is that the concentration of hyperpolarized lactate in the blood after injection is similar to that seen in an Leonurine site exercising animal; this differentiates it from hyperpolarized pyruvate, which is injected at a concentration that is much higher than is found endogenously.[2-13C]-fructoseOwing to the limited lifetime of the hyperpolarized nucleus, with signal decay dependent on T 1 relaxation, carboxylate carbons have been the primary targets for development of hyperpolarized metabolic probes. The use of these carbon nuclei makes it difficult to investigate upstream glycolytic processes, which have been related to both cancer metabolism as well as other metabolic abnormalities, such as fatty liver disease and diabetes. Glucose carbons have short T 1’s (<1 second) and therefore cannot be used as an in vivo hyperpolarized metabolic probe of glycolysis. However, the pentose analog fructose can also enter glycolysis through its phosphorylation by hexokinase and yield complementary information. The C2 of fructose is a hemiketal that has a relatively longer relaxation time (16 seconds at 37 ) and high solution state polarization (12 ) [143]. Injection of hyperpolarized [2-13C]-fructose into the TRAMP model demonstrated differences in uptake and metabolism in regions of prostate cancer relative to surrounding benign abdominal tissues [143].[5-13C]glutamineGlutamine is important for tumor growth, and in many cell lines, its utilization is positively correlated with cell proliferation. Imaging gluta-Neoplasia Vol. 13, No. 2,Cancer Metabolism by Imaging Hyperpolarized NucleiKurhanewicz et al.[1-13C]succinateSuccinic acid has been hyperpolarized using PHIP [81]. Recently, real-time metabolism of the molecule has been demonstrated in vivo [144]. Furthermore, succinate can induce hypertension in animals when administered intravenously [145]; it is unclear whether this effect occurs in humans, but if it does, this may limit its clinical application. -Ketoisocaproate (KIC) is metabolized to leucine by the enzyme branched-chain amino acid transferase (BCAT), which is found to be upregulated in some tumors. BCAT is a putative marker for metastasis and a target for the proto-oncogene c-myc. Injection of hyperpolarized [1-13C]KIC into rodents have shown ample conversion into leucine [146]. In a preclinical study, the SNR and contrast were compared between hyperpolarized [1-13C]pyruvate and [1-13C]-KIC. Here, sim.