Ge tumors and metastases. (B) Axial T2weighted 1H image depicting the primary tumor and lymph node metastasis from a TRAMP mouse using a late-stage key tumor along with the overlay of hyperpolarized [1-13C]lactate image after the injection of 350 l of hyperpolarized [1-13C]pyruvate. Hyperpolarized [1-13C] lactate increased in going from regular to prostate cancer and with disease progression. (C) A box plot quantitatively summarizing the peak area-to-noise ratios in the [1-13C]lactate-to-noise ratio for the four histologically defined groups. The lactate peak region SNR values had been statistically distinctive (P < .05) for all four groups, except that early stage tumors were not significantly different from lymph node metastases. In addition, there was minimal overlap between individual [1-13C]lactate-to-noise ratios between normal prostates and early and late-stage tumors. Figure adapted from Albers et al. [123].Cancer Metabolism by Imaging Hyperpolarized NucleiKurhanewicz et al.Neoplasia Vol. 13, No. 2,Figure 3. (A) Transverse proton MR image of a mouse with a subcutaneously implanted EL4 tumor (outlined in red). (B) pH map of the same animal calculated from the ratio of the H13CO3 acquired 10 seconds after intravenous injection of 100 mM hyperpolarized H13CO3- and assuming a pK a of 6.17 (pH = pK a + log ([HCO3] / [CO2]). Figure adapted from Gallagher et al. [137].abundant in tissue (25 mM) and is already infused into patients at concentrations that would be needed for a hyperpolarized 13C imaging measurement of tissue pH.[1,4-13C2 ]fumarateAfter intravenous injection of hyperpolarized [1,4-13C2]fumarate, its metabolism to hyperpolarized [1,4-13C2]malate, catalyzed by the enzyme fumarase, has been demonstrated in tumors and skeletal muscle [138]. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/20732896 The signal from hyperpolarized malate enhanced considerably in skeletal muscle right after ischemia and reperfusion [138], suggesting that it might be used as a optimistic contrast agent for identifying ischemic injury. The accumulation of malate was suggested to become because of a block in the TCA cycle [138]. Even so, current research in drug-treated tumors have demonstrated that the accumulation of malate is because of cellular necrosis [139]. In viable cells, the transport rate of fumarate into the mitochondria is too slow to enable the observation of labeled malate inside the lifetime with the polarization. Having said that, if this permeability barrier is removed, because it is in necrotic cells, then fumarate conversion to malate can be observed. Fumarate is potentially a beneficial agent for detecting treatment response in tumors because the production of labeled malate would seem to be an unequivocal order BAY1217389 indicator of cell death.mine metabolism could, as a result, be a marker of tumor growth and division and is currently safely administered to humans within the clinic. The conversion of hyperpolarized [5-13C]glutamine to [5-13C]glutamate, catalyzed by intramitochondrial glutaminase, has been demonstrated in hepatocellular carcinoma cells in vitro [141]. The label in the C-5 position shows a larger chemical shift right after conversion to glutamate compared with the C-1 position, which aids detection of the metabolite, even though the T 1 is slightly shorter. The comparatively low levels of polarization obtained in this study precluded studies in vivo. Having said that, with larger levels of polarization, it may be attainable to work with this substrate to assess the effects of tumor treatment with cytostatic drugs.[1-13C]acetateAfter injection of hyperpolarized [1-13C]acetat.