Ge tumors and metastases. (B) Axial T2weighted 1H image depicting the primary tumor and lymph

Ge tumors and metastases. (B) Axial T2weighted 1H image depicting the primary tumor and lymph node metastasis from a TRAMP mouse having a late-stage principal tumor along with the overlay of Niraparib metabolite M1 hyperpolarized [1-13C]lactate image following the injection of 350 l of hyperpolarized [1-13C]pyruvate. Hyperpolarized [1-13C] lactate enhanced in going from regular to prostate cancer and with illness progression. (C) A box plot quantitatively summarizing the peak area-to-noise ratios in the [1-13C]lactate-to-noise ratio for the 4 histologically defined groups. The lactate peak location SNR values were statistically unique (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 elevated considerably in skeletal muscle right after ischemia and reperfusion [138], suggesting that it may be employed as a positive contrast agent for identifying ischemic injury. The accumulation of malate was recommended to be resulting from a block in the TCA cycle [138]. Having said that, recent studies in drug-treated tumors have demonstrated that the accumulation of malate is as a result of cellular necrosis [139]. In viable cells, the transport rate of fumarate in to the mitochondria is too slow to allow the observation of labeled malate inside the lifetime in the polarization. Nevertheless, if this permeability barrier is removed, because it is in necrotic cells, then fumarate conversion to malate could be observed. Fumarate is potentially a helpful agent for detecting therapy response in tumors since the production of labeled malate would appear to be an unequivocal indicator of cell death.mine metabolism could, therefore, be a marker of tumor development and division and is already safely administered to humans inside 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 after conversion to glutamate compared using the C-1 position, which aids detection of the metabolite, although the T 1 is slightly shorter. The reasonably low levels of polarization obtained in this study precluded studies in vivo. Nevertheless, with greater levels of polarization, it might be probable to make use of this substrate to assess the effects of tumor remedy with cytostatic drugs.[1-13C]acetateAfter injection of hyperpolarized [1-13C]acetat.