Hyperpolarising Pyruvate through Signal Amplification by Reversible Exchange (SABRE)

Abstract

Hyperpolarisation methods that premagnetise agents such as pyruvate are currently receiving significant attention because they produce sensitivity gains that allowd isease tracking and interrogation of cellular metabolism by magnetic resonance.Here,wecommunicate how signal amplification by reversible exchange (SABRE) can providestrong 13 Cpyruvate signal enhancements in seconds through the formation of the novel polarisation transfer catalyst [Ir(H) 2 (h 2 -pyruvate)-(DMSO)(IMes)].B yh arnessing SABRE, strong signals for [1-13 C]-and [2-13 C]pyruvate in addition to along-lived singlet state in the [1,2-13 C 2 ]form are readily created;the latter can be observed five minutes after the initial hyperpolarisation step. We also demonstrate how this development may help with future studies of chemical reactivity.

Biomedical Applications of the Dynamic Nuclear Polarization and Parahydrogen Induced Polarization Techniques for Hyperpolarized ¹³C MR Imaging

“…The latter two methods have been demonstrated for biomedical 13 C molecular MRI applications and these form the focus of this review article. We note that signal amplification by reversible exchange (SABRE), 13 closely-related to conventional PHIP, is recently showing progress toward potential in vivo application 14 but will not be covered in this article as biomedical application is yet to be shown; we refer the reader to Robertson and Mewis 15 for an up-to-date review.…”

“…Finally, the SABRE parahydrogen method, wherein polarization transfer occurs by reversible exchange and the target molecule remains chemically unaltered upon interaction with parahydrogen, has the potential yield heteronuclear ( 13 C, 15 N) hyperpolarization on a broader range of molecular imaging probes than conventional PHIP and may lead to several unprecedented avenues of biomedical application. 162 Although to date no in vivo experiments have been performed with SABRE-polarized probes, the recent demonstration of both hyperpolarized [1-13 C] and [2-13 C]pyruvate, 14 although at relatively low polarizations, represents a significant step toward biomedical application.…”

Generalised magnetisation-to-singlet-order transfer in nuclear magnetic resonance

“…This is not always true. In the general case, the best one can do is to set the optimal echo number n* as follows n* = round(p/(2x 12 )) (27) so that eqn (26) is approximately satisfied. The two echo trains of the M2S sequence are separated by a 90 x pulse followed by a free evolution interval of duration t 2 .…”

“…[13][14][15][16][17] For the field of hyperpolarisation NMR long-lived spin modes represent promising candidates for the ''storage'' of an enhanced magnetic response, and its readout at convenient times. [18][19][20][21][22][23][24][25][26][27][28] More recently, techniques of this type have been applied to the study of bio-molecular markers and their intricate interactions with their surroundings. [29][30][31][32][33][34] Many experiments in singlet-assisted NMR exploit nearequivalent spin-1/2 pairs, meaning that the difference in chemically shifted resonance frequencies for the two spins D is much smaller than the scalar coupling constant J (both D and J are defined in Hz).…”

“…37,38 We therefore anticipate its incorporation into a wide class of singlet-assisted NMR experiments. [15][16][17][25][26][27][28][31][32][33][34] Further extensions to the case of heteronuclear spin systems are feasible, for example in the context of parahydrogenenhanced NMR. [63][64][65]…”