Parahydrogen Induced Polarization of 1-13C-Phospholactate-d2 for Biomedical Imaging with &gt;30,000,000-fold NMR Signal Enhancement in Water

Shchepin, Roman V.; Coffey, Aaron M.; Waddell, Kevin W.; Chekmenev, Eduard Y.

doi:10.1021/ac500952z

Cited by 84 publications

(155 citation statements)

References 37 publications

(104 reference statements)

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“…As far as biomedical applications are concerned, few molecules have been hyperpolarized by means of this method. Among them, succinate 14,15 and phospho-lactate 16,17 are the only metabolites for which good hyperpolarization level has been achieved until now. Alternative routes have been proposed to achieve PHIP on biologically relevant molecules by functionalizing the substrates of interest with moieties capable of hydrogenation [18][19][20] .…”

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confidence: 99%

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

2015

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The advent of nuclear spins hyperpolarization techniques represents a breakthrough in the field of medical diagnoses by magnetic resonance imaging. Dynamic nuclear polarization (DNP) is the most widely used method, and hyperpolarized metabolites such as [1-13 C]-pyruvate are shown to report on status of tumours. Parahydrogen-induced polarization (PHIP) is a chemistry-based technique, easier to handle and much less expensive in respect to DNP, with significantly shorter polarization times. Its main limitation is the availability of unsaturated precursors for the target substrates; for instance, acetate and pyruvate cannot be obtained by direct incorporation of the parahydrogen molecule. Herein we report a method that allows us to achieve hyperpolarization in this kind of molecule by means of a tailored precursor containing a hydrogenable functionality that, after polarization transfer to the target 13 C moiety, is cleaved to obtain the metabolite of interest. The reported procedure can be extended to a number of other biologically relevant substrates.

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confidence: 99%

ParaHydrogen Induced Polarization of 13C carboxylate resonance in acetate and pyruvate

2015

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“…In many cases this precursor does not exist or is not stable. Even in cases where a suitable precursor exists (e.g., for pyruvate or acetate), care must be taken to ensure that only the desired hydrogenation end-product is produced [89–91]. Furthermore, the couplings between the nucleus to be hyperpolarized and the para proton pair must differ by an amount that is large compared to other couplings to the target nucleus [92].…”

Section: Hyperpolarized Mrimentioning

confidence: 99%

The use of hyperpolarized carbon-13 magnetic resonance for molecular imaging

Siddiqui

Kadlecek

Pourfathi

et al. 2017

Advanced Drug Delivery Reviews

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Until recently, molecular imaging using magnetic resonance (MR) has been limited by the modality’s low sensitivity, especially with non-proton nuclei. The advent of hyperpolarized (HP) MR overcomes this limitation by substantially enhancing the signal of certain biologically important probes through a process known as external nuclear polarization, enabling real-time assessment of tissue function and metabolism. The metabolic information obtained by HP MR imaging holds significant promise in the clinic, where it could play a critical role in disease diagnosis and therapeutic monitoring. This review will provide a comprehensive overview of the developments made in the field of hyperpolarized MR, including advancements in polarization techniques and delivery, probe development, pulse sequence optimization, characterization of healthy and diseased tissues, and the steps made towards clinical translation.

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“…This can be accomplished by cooling hydrogen gas and then inducing ortho-to-para conversion via an ironoxide or charcoal catalyst (Natterer and Bargon, 1997). Recently, it was reported that by using PHIP, 13 C nuclear spin polarization of 1-13 C-phospholactate-d 2 was increased by >30,000,000-fold in water (Shchepin et al, 2014a). PHIP polarization of 1-13 Cphospholactate potentially enables the in vivo administration of a hydrogenated hyperpolarized adduct which is metabolized to 1-13 C-lactate by blood phosphatases in a mucin 1 mouse model of breast cancer and visualized by high-resolution 13 C NMR.…”

Section: Magnetic Resonancementioning

confidence: 99%