In vivo and in vitro liver cancer metabolism observed with hyperpolarized [5-13C]glutamine

Optimizing dissolution dynamic nuclear polarization

“…13 C was chosen as a target nuclear spin because (1) carbon is present in almost all relevant molecules in biology, (2) isotope labeling is often affordable, (3) the thermal equilibrium background signal of 13 C in vivo is below detection limit and therefore not interfering, in contrast to 1 H, and (4) quaternary carbons have relatively long T 1 's in liquid state at room temperature after dissolution so that the hyperpolarization can survive on sufficiently long timescales to probe relevant bio-chemical processes. Trityl radicals, a class of radicals with narrow ESR lines, are especially suited for the direct polarization of 13 C [3,7,8]. The two key parameters that describe the DNP efficiency of a free radical are (1) the maximum polarization P ( 13 C) achievable and (2) the time constant s DNP ( 13 C) of the approach to the DNP equilibrium.…”

“…D-DNP has rapidly found a 'killer' application in in vivo MRI. The high signal-to-noise ratio provided by d-DNP for 13 C labeled molecules has enabled the observation of hyperpolarized [1][2][3][4][5][6][7][8][9][10][11][12][13] C pyruvate in humans shortly after infusion, and its enzymatic in-cello conversion into 1-…”

“…A straightforward and low-cost alternative consists in using one of the widely available nitroxide radicals, such as TEMPO (2,2,6,6-tetramethylpiperidine 1-oxyl) or TEMPOL (4-Hydroxy TEMPO). Unfortunately, because of their broad ESR lines, nitroxide radicals are poor agents for direct polarization of 13 C under the conditions of temperatures and magnetic fields (typically T = 1.2 K and B 0 = 3.35 T) that are often used for trityl. Direct 13 C polarization using nitroxide radicals typically yields disappointing levels near P( 13 C) = 10%, though with relatively short (Fig.…”

“…The pyruvate uptake and its conversion is faster in cancer cells than in healthy tissues [11], which opens new perspectives for cancer diagnosis, in particular for prostate cancer. This has led to the detection of prostate tumours by localized 13 C spectroscopy in human patients [12]. Such clinical applications call for the development of DNP polarizers that are specially designed for clinical applications, fulfilling specific requirements such as sterility [9].…”

“…Although most peer-reviewed papers utilizing d-DNP are concerned with localized spectroscopy or imaging of tumours following the infusion of hyperpolarized 1-13 C pyruvate, the technology of d-DNP can in principle be used in combination with a variety of other NMR or MRI experiments, using an extensive diversity of molecules, and addressing many other nuclear spins. One can cite amongst many other publications in vitro or in-cell studies [13,14], drug screening [15], and monitoring of chemical reactions including the detection of intermediates [16]. Further d-DNP NMR applications can be found in reference [17].…”