We describe a novel (13)C enriched precursor molecule, sodium 1-(13)C acetylenedicarboxylate, which after hydrogenation by PASADENA (Parahydrogen and Synthesis Allows Dramatically Enhanced Nuclear Alignment) under controlled experimental conditions, becomes hyperpolarized (13)C sodium succinate. Fast in vivo 3D FIESTA MR imaging demonstrated that, following carotid arterial injection, the hyperpolarized (13)C-succinate appeared in the head and cerebral circulation of normal and tumor-bearing rats. At this time, no in vivo hyperpolarized signal has been localized to normal brain or brain tumor. On the other hand, ex vivo samples of brain harvested from rats bearing a 9L brain tumor, 1 h or more following in vivo carotid injection of hyperpolarized (13)C sodium succinate, contained significant concentrations of the injected substrate, (13)C sodium succinate, together with (13)C maleate and succinate metabolites 1-(13)C-glutamate, 5-(13)C-glutamate, 1-(13)C-glutamine and 5-(13)C-glutamine. The (13)C substrates and products were below the limits of NMR detection in ex vivo samples of normal brain consistent with an intact blood-brain barrier. These ex vivo results indicate that hyperpolarized (13)C sodium succinate may become a useful tool for rapid in vivo identification of brain tumors, providing novel biomarkers in (13)C MR spectral-spatial images.
Purpose The purpose of this study was to characterize tissue-specific alterations in metabolism of hyperpolarized (HP) gluconeogenic precursors 13C-lactate and 13C-pyruvate by rat liver and kidneys under conditions of fasting or insulin-deprived diabetes. Methods Seven normal rats were studied by MR spectroscopic imaging of both HP 13C-lactate and 13C-pyruvate in both normal fed and 24 h fasting states, and seven additional rats were scanned after induction of diabetes by streptozotocin (STZ) with insulin withdrawal. Phosphoenolpyruvate carboxykinase (PEPCK) expression levels were also measured in liver and kidney tissues of the STZ-treated rats. Results Multiple sets of significant signal modulations were detected, with graded intensity in general between fasting and diabetic states. An approximate two-fold reduction in the ratio of 13C-bicarbonate to total 13C signal was observed in both organs in fasting. The ratio of HP lactate-to-alanine was markedly altered, ranging from a liver-specific 54% increase in fasting, to increases of 69% and 92% in liver and kidney, respectively, in diabetes. Diabetes resulted in a 40% increase in renal lactate signal. STZ resulted in 5.86-fold and 2.73-fold increases in PEPCK expression in liver and kidney, respectively. Conclusion MRI of HP 13C gluconeogenic precursors may advance diabetes research by clarifying organ-specific roles in abnormal diabetic metabolism.
The 13C n.m.r. spectra of several norbornyl derivatives have been recorded to examine the variation of I3C shieldings with molecular geometry. Since it is well established that nonbonded interactions between vicinal carbon nuclei lead to pronounced upfield shifts, the so-called y effects, series of methyl-substituted norbornanes, norbornenes, norbornan-2-ones (norcamphors), and norborn-5-en-2-ones were prepared a s model systems having a variety of y interactions between vicinal methyl groups. The observed shifts of these methyl carbons are considered in terms of the dihedral angle relating the vicinal nuclei. The use of specific deuterationfor unequivocal signal assignments ofcarbons geminal and vicinal to the site of deuteration is illustrated.Les spectres 1.m.n. I3C de plusieurs derives du norbornyle ont ete enregistres afin d'etudier la variation de I'effet de blindage du I3C en fonction de la geometrie moleculaire. Puisqu'il est bien connu que d e s interactions non-likes entre des carbones vicinaux entrainent des deplacements du signal vers des champs Cleves, relation connue sous le nom effets-y plusieurs norbornanes, norbornenes, norbornanones-2 (norcamphres) et norbornkne-5 ones-2 substituis par des groupes methyles ont i t 6 prCpares afin de servir d e modkles posskdant diffkrentes interactions y entre des groupes methyles vicinaux. O n a utilis6 la deutCration spicifique pour attribuer sans arnbiguite les signaux se rattachant aux carbones gCmines et vicinaux au site d e deuteration.[Traduit par le journal]Can. J . Chem., 51, 2893Chem., 51, (1973
The I3C spectra of 16 methyl substituted cyclohexanones and 15 methylcyclopentanones have been determined. These series were chosen as model systems for the study of steric and conformation effects on I3C shieldings. Con~plete assignments of the individual signals were accomplished by intercomparison of the shielding data within each series and the trends observed are readily interpreted in conformational terms. Each of the cyclohexanones exists preferentially in chair conformations although there is evidence of ring distortion in the tetramethyl derivatives. The cyclopentanones apparently strongly favor half-chair forms with maximum puckering at C-3 and C-4. In general, shielding differences between cis and t~.ntts isomers are pronounced and the assignment of stereochemistry for some cis-trnrlsdimethyl derivatives is illustrated.Further examples of marked rlesl~ieldit~g trends associated with sterically crowded 6 nuclei in syrz-axial arrangements are described. IntroductionThe res~llts of carbon-13 n.ni.r. st~tdies of a variety of cyclic systems have established that 13C spectroscopy is a p o w e r f~~l method for stereochelnical assignments and confor~national analysis (1). Several six-membered ring systems, both mono-and polycyclic, have been examined in detail and in general it is found that axial substituents tend t o shield the neighboring carbons (C-1, -2, -3, -5, and -6 in a monosubstituted cyclohexane) relative to their positions in the spectrum of the equatorial analogs. The variation of carbon shieldings with substitution in simple five-membered ring derivatives has received much less attention. Apart from studies of a variety of norbornyl derivatives (2) the only detailed examinations of cyclopentane derivatives is that of Christ1 et al. (3) in which several methylcyclopentanes, cyclopentanols, and cyclopentyl acetates were studied. We wish t o report the results of a 13C n.m.r. investigation of
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