Friday, January 30, 2015

High-resolution 3D proton MRI of hyperpolarized gas enabled by parahydrogen and Rh/TiO2 heterogeneous catalyst


Kovtunov, K.V., et al., High-resolution 3D proton MRI of hyperpolarized gas enabled by parahydrogen and Rh/TiO2 heterogeneous catalyst. Chemistry, 2014. 20(37): p. 11636-9.


Several supported metal catalysts were synthesized, characterized, and tested in heterogeneous hydrogenation of propene with parahydrogen to maximize nuclear spin hyperpolarization of propane gas using parahydrogen induced polarization (PHIP). The Rh/TiO2 catalyst with a metal particle size of 1.6 nm was found to be the most active and effective in the pairwise hydrogen addition and robust, demonstrating reproducible results with multiple hydrogenation experiments and stability for >/=1.5 years. 3D (1) H magnetic resonance imaging (MRI) of 1 % hyperpolarized flowing gas with microscale spatial resolution (625x625x625 mum(3) ) and large imaging matrix (128x128x32) was demonstrated by using a preclinical 4.7 T scanner and 17.4 s imaging scan time.

Wednesday, January 28, 2015

In vivo Overhauser-enhanced MRI of proteolytic activity


Koonjoo, N., et al., In vivo Overhauser-enhanced MRI of proteolytic activity. Contrast Media Mol Imaging, 2014. 9(5): p. 363-71.


There is an increasing interest in developing novel imaging strategies for sensing proteolytic activities in intact organisms in vivo. Overhauser-enhanced MRI (OMRI) offers the possibility to reveal the proteolysis of nitroxide-labeled macromolecules thanks to a sharp decrease of the rotational correlation time of the nitroxide moiety upon cleavage. In this paper, this concept is illustrated in vivo at 0.2 T using nitroxide-labeled elastin orally administered in mice. In vitro, this elastin derivative was OMRI-visible and gave rise to high Overhauser enhancements (19-fold at 18 mm nitroxide) upon proteolysis by pancreatic porcine elastase. In vivo three-dimensional OMRI detection of proteolysis was carried out. A keyhole fully balanced steady-state free precession sequence was used, which allowed 3D OMRI acquisition within 20 s at 0.125 mm(3) resolution. About 30 min after mouse gavage, proteolysis was detected in the duodenum, where Overhauser enhancements were 7.2 +/- 2.4 (n = 7) and was not observed in the stomach. Conversely, orally administered free nitroxides or pre-digested nitroxide-labeled elastin were detected in the mouse's stomach by OMRI. Combined with specific molecular probes, this Overhauser-enhanced MRI technique can be used to evaluate unregulated proteolytic activities in various models of experimental diseases and for drug testing.

Monday, January 26, 2015

Apparent rate constant mapping using hyperpolarized [1–13C]pyruvate


Khegai, O., et al., Apparent rate constant mapping using hyperpolarized [1–13C]pyruvate. NMR in Biomedicine, 2014. 27(10): p. 1256-1265.


Hyperpolarization of [1-13C]pyruvate in solution allows real-time measurement of uptake and metabolism using MR spectroscopic methods. After injection and perfusion, pyruvate is taken up by the cells and enzymatically metabolized into downstream metabolites such as lactate, alanine, and bicarbonate. In this work, we present comprehensive methods for the quantification and interpretation of hyperpolarized 13C metabolite signals. First, a time-domain spectral fitting method is described for the decomposition of FID signals into their metabolic constituents. For this purpose, the required chemical shift frequencies are automatically estimated using a matching pursuit algorithm. Second, a time-discretized formulation of the two-site exchange kinetic model is used to quantify metabolite signal dynamics by two characteristic rate constants in the form of (i) an apparent build-up rate (quantifying the build-up of downstream metabolites from the pyruvate substrate) and (ii) an effective decay rate (summarizing signal depletion due to repetitive excitation, T1-relaxation and backward conversion). The presented spectral and kinetic quantification were experimentally verified in vitro and in vivo using hyperpolarized [1-13C]pyruvate. Using temporally resolved IDEAL spiral CSI, spatially resolved apparent rate constant maps are also extracted. In comparison to single metabolite images, apparent build-up rate constant maps provide improved contrast by emphasizing metabolically active tissues (e.g. tumors) and suppression of high perfusion regions with low conversion (e.g. blood vessels). Apparent build-up rate constant mapping provides a novel quantitative image contrast for the characterization of metabolic activity. Its possible implementation as a quantitative standard will be subject to further studies. Copyright © 2014 John Wiley & Sons, Ltd.

Facility Manager - 600MHz DNP MAS NMR Facility University of Nottingham, UK

From the Ampere Magnetic Resonance List

FACILITY MANAGER - 600MHz DNP MAS NMR Spectrometer University of Nottingham 

Salary: £37394 to £45954 per annum, depending on skills and experience. Salary progression beyond this scale is subject to performance.


Applications are invited from suitably qualified candidates for the post of Facility Manager for the new Dynamic Nuclear Polarization (DNP) Magic Angle Spinning (MAS) NMR Facility at the University of Nottingham. The Nottingham DNP MAS NMR Facility will be established in 2015 and is supported by £3.1M of funding from the EPSRC and the University of Nottingham. The Facility is operated jointly by the Schools of Chemistry, Life Sciences, and Physics and Astronomy and is directed by Drs. Boyan Bonev, Walter Köckenberger and Jeremy Titman. The Facility’s instrumentation will be housed in the Sir Peter Mansfield Magnetic Resonance Centre at the University and comprises a 600 MHz DNP MAS NMR spectrometer equipped with low-temperature triple- and double-resonance 3.2 mm MAS probes covering Larmor frequencies from 1H to 109Ag.

The Facility Manager will be responsible for the operation of the Facility’s instrumentation, carrying out routine maintenance when necessary. The role involves making DNP MAS NMR measurements on behalf of internal and external collaborators and providing support, guidance and supervision for Facility users with all aspects of DNP MAS NMR. The Facility Manager will be expected to develop collaborations with Facility users and to assist them with grant applications. In addition the role involves marketing the Facility, for example by maintaining the website, writing annual reports and attending conferences. There will be an opportunities for the Facility Manager to develop an individual programme of research in DNP MAS NMR.

Candidates must hold a relevant PhD in physics, chemistry or life sciences (or a related subject). Candidates must have experience of developing and implementing a wide range of advanced solid-state NMR experiments and of applying solid-state NMR to materials or biological systems. Experience in DNP NMR, in maintaining NMR instrumentation and in managing a major research project will be an advantage. In addition, candidates will need excellent communication skills and the ability to interact with researchers in other fields.

This full-time post is available from April 2015 on a fixed term contract for 4 years (An extension will depend on internal review of the operation of the facility)

The University of Nottingham values diversity and is committed to equality of opportunity.

Informal enquiries may be addressed to Walter Kockenberger, tel: 0115 9515161 or email: 

walter.kockenberger@nottingham.ac.uk. (Please note that applications sent directly to this email address will not be accepted.)

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Friday, January 23, 2015

Hyperpolarized [1,3-(13) C2 ]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer


Jensen, P.R., et al., Hyperpolarized [1,3-(13) C2 ]ethyl acetoacetate is a novel diagnostic metabolic marker of liver cancer. Int J Cancer, 2015. 136(4): p. E117-26.


An increased prevalence of liver diseases such as hepatitis C and nonalcoholic fatty liver results in an augmented incidence of the most common form of liver cancer, hepatocellular carcinoma (HCC). HCC is most often found in the cirrhotic liver and it can therefore be challenging to rely on anatomical information alone when diagnosing HCC. Valuable information on specific cellular metabolism can be obtained with high sensitivity thanks to an emerging magnetic resonance (MR) technique that uses (13) C labeled hyperpolarized molecules. Our interest was to explore potential new high contrast metabolic markers of HCC using hyperpolarized (13) C-MR. This work led to the identification of a class of substrates, low molecular weight ethyl-esters, which showed high specificity for carboxyl esterases and proved in many cases to possess good properties for signal enhancement. In particular, hyperpolarized [1,3-(13) C2 ]ethyl acetoacetate (EAA) was shown to provide a metabolic fingerprint of HCC. Using this substrate a liver cancer implanted in rats was diagnosed as a consequence of an approximately 4 times higher metabolic substrate-to-product ratio than in the surrounding healthy tissue, (p = 0.009). Unregulated cellular uptake as well as cosubstrate independent enzymatic conversion of EAA, made this substrate highly useful as a hyperpolarized (13) C-MR marker. This could be appreciated by the signal-to-noise (SNR) obtained from EAA, which was comparable to the SNR reported in a literature liver cancer study with state-of-the-art hyperpolarized substrate, [1-(13) C]pyruvate. Also, the contrast-to-noise (CNR) in the EAA based metabolic ratio images was significantly improved compared with the CNR in equivalent images reported using [1-(13) C]pyruvate.

Wednesday, January 21, 2015

[NMR] postdoctoral research positions in the Tycko lab at NIH

From the Ampere Magnetic Resonance List

Several openings for new postdocs in the Tycko lab are expected in 2015. Research areas include: (1) structural studies of HIV-1 proteins by solid state NMR; (2) DNP-enhanced studies of intermediates in protein folding, protein aggregation, and protein-protein recognition processes; (3) DNP-enhanced magnetic resonance imaging; (4)structural/ biophysical/ mechanistic studies of amyloid fibrils associated with Alzheimer's disease. In addition, the lab has a long-standing interest in new NMR methodology, including pulse sequences, data analysis, and equipment. Candidates must have received a Ph.D. within the past four years. Candidates with strong backgrounds in the construction of experimental apparatus, or biochemical/biological techniques, or sophisticated spectroscopy are encouraged to apply. Please send your CV, your publication list, and a description of your research accomplishments to Rob Tycko at robertty@mail.nih.gov

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Chemical-Shift-Resolved19F NMR Spectroscopy between 13.5 and 135 MHz: Overhauser-DNP-Enhanced Diagonal Suppressed Correlation Spectroscopy


George, C. and N. Chandrakumar, Chemical-Shift-Resolved19F NMR Spectroscopy between 13.5 and 135 MHz: Overhauser-DNP-Enhanced Diagonal Suppressed Correlation Spectroscopy. Angewandte Chemie, 2014. 126(32): p. 8581-8584.


Overhauser–DNP-enhanced homonuclear 2D 19F correlation spectroscopy with diagonal suppression is presented for small molecules in the solution state at moderate fields. Multi-frequency, multi-radical studies demonstrate that these relatively low-field experiments may be operated with sensitivity rivalling that of standard 200–1000 MHz NMR spectroscopy. Structural information is accessible without a sensitivity penalty, and diagonal suppressed 2D NMR correlations emerge despite the general lack of multiplet resolution in the 1D ODNP spectra. This powerful general approach avoids the rather stiff excitation, detection, and other special requirements of high-field 19F NMR spectroscopy.

Friday, January 16, 2015

Chemical-Shift-Resolved19F NMR Spectroscopy between 13.5 and 135 MHz: Overhauser-DNP-Enhanced Diagonal Suppressed Correlation Spectroscopy


George, C. and N. Chandrakumar, Chemical-Shift-Resolved19F NMR Spectroscopy between 13.5 and 135 MHz: Overhauser-DNP-Enhanced Diagonal Suppressed Correlation Spectroscopy. Angewandte Chemie, 2014. 126(32): p. 8581-8584.


Overhauser–DNP-enhanced homonuclear 2D 19F correlation spectroscopy with diagonal suppression is presented for small molecules in the solution state at moderate fields. Multi-frequency, multi-radical studies demonstrate that these relatively low-field experiments may be operated with sensitivity rivalling that of standard 200–1000 MHz NMR spectroscopy. Structural information is accessible without a sensitivity penalty, and diagonal suppressed 2D NMR correlations emerge despite the general lack of multiplet resolution in the 1D ODNP spectra. This powerful general approach avoids the rather stiff excitation, detection, and other special requirements of high-field 19F NMR spectroscopy.

Wednesday, January 14, 2015

COST Meeting on "Paramagnetic relaxation and spin hyperpolarization"

From the Ampere Magnetic Resonance List

Dear colleagues, 

It is a great pleasure to announce the COST Meeting on Paramagnetic relaxation and spin hyperpolarization, which will be held at Institut Henry Poincare (Paris, France) on May 4-6, 2015.

This meeting is organized within the framework of the EU COST Action TD1103 "Hyperpolarization Physics and Methodology in NMR and MRI" (www.eurohyperpol.eu). It is a discussion meeting that joins two COST working groups: "Theory" (WG2) and "Relaxation" (WG3).

The meeting will be focused on spin relaxation processes in paramagnetic systems and their role in spin hyperpolarization experiments. Introductory talks of didactic character will be given by well-known specialists in the field:

  • Prof. Geoffrey Bodenhausen (EPFL Lausanne, Switzerland; Ecole Normale Superieure, Paris, France)
  • Dr. Giuseppe Pileio (University of Southampton, UK)
  • Prof. Thomas Prisner (Goethe University of Frankfurt am Main, Germany)
  • Prof. Shimon Vega (Weizmann Institute of Science, Rehovot, Israel)
In addition, several oral contributions on the progress in the field are welcome with preference to early-stage researchers. The planned number of participants will guarantee lively discussions and informal communication.

You can find more information concerning accommodation, registration and program on the web-site of the meeting: http://lptms.u-psud.fr/workshop/prash/overview


On behalf of the organizing committee,
Konstantin Ivanov.

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Real-time cardiac metabolism assessed with hyperpolarized [1-13C]acetate in a large-animal model


Flori, A., et al., Real-time cardiac metabolism assessed with hyperpolarized [1-13C]acetate in a large-animal model. Contrast Media & Molecular Imaging, 2014: p. n/a-n/a.


Dissolution-dynamic nuclear polarization (dissolution-DNP) for magnetic resonance (MR) spectroscopic imaging has recently emerged as a novel technique for noninvasive studies of the metabolic fate of biomolecules in vivo. Since acetate is the most abundant extra- and intracellular short-chain fatty acid, we focused on [1-13C]acetate as a promising candidate for a chemical probe to study the myocardial metabolism of a beating heart. The dissolution-DNP procedure of Na[1-13C]acetate for in vivo cardiac applications with a 3 T MR scanner was optimized in pigs during bolus injection of doses of up to 3 mmol. The Na[1-13C]acetate formulation was characterized by a liquid-state polarization of 14.2% and a T1Eff in vivo of 17.6 ± 1.7 s. In vivo Na[1-13C]acetate kinetics displayed a bimodal shape: [1-13C]acetyl carnitine (AcC) was detected in a slice covering the cardiac volume, and the signal of 13C-acetate and 13C-AcC was modeled using the total area under the curve (AUC) for kinetic analysis. A good correlation was found between the ratio AUC(AcC)/AUC(acetate) and the apparent kinetic constant of metabolic conversion, from [1-13C]acetate to [1-13C]AcC (kAcC), divided by the AcC longitudinal relaxation rate (r1). Our study proved the feasibility and the limitations of administration of large doses of hyperpolarized [1-13C]acetate to study the myocardial conversion of [1-13C]acetate in [1-13C]acetyl-carnitine generated by acetyltransferase in healthy pigs. Copyright © 2014 John Wiley & Sons, Ltd.

Monday, January 12, 2015

Quantitative Trace Analysis of Complex Mixtures Using SABRE Hyperpolarization


Eshuis, N., et al., Quantitative Trace Analysis of Complex Mixtures Using SABRE Hyperpolarization. Angew Chem Int Ed Engl, 2014: p. n/a-n/a.


Signal amplification by reversible exchange (SABRE) is an emerging nuclear spin hyperpolarization technique that strongly enhances NMR signals of small molecules in solution. However, such signal enhancements have never been exploited for concentration determination, as the efficiency of SABRE can strongly vary between different substrates or even between nuclear spins in the same molecule. The first application of SABRE for the quantitative analysis of a complex mixture is now reported. Despite the inherent complexity of the system under investigation, which involves thousands of competing binding equilibria, analytes at concentrations in the low micromolar range could be quantified from single-scan SABRE spectra using a standard-addition approach.

Friday, January 9, 2015

HyperBIRD: A Sensitivity-Enhanced Approach to Collecting Homonuclear-Decoupled Proton NMR Spectra


Donovan, K.J. and L. Frydman, HyperBIRD: A Sensitivity-Enhanced Approach to Collecting Homonuclear-Decoupled Proton NMR Spectra. Angew Chem Int Ed Engl, 2014: p. n/a-n/a.


Samples prepared following dissolution dynamic nuclear polarization (DNP) enable the detection of NMR spectra from low-gamma nuclei with outstanding sensitivity, yet have limited use for the enhancement of abundant species like 1 H nuclei. Small- and intermediate-sized molecules, however, show strong heteronuclear cross-relaxation effects: spontaneous processes with an inherent isotopic selectivity, whereby only the 13 C-bonded protons receive a polarization enhancement. These effects are here combined with a recently developed method that delivers homonuclear-decoupled 1 H spectra in natural abundance samples based on heteronuclear couplings to these same, 13 C-bonded nuclei. This results in the HyperBIRD methodology; a single-shot combination of these two effects that can simultaneously simplify and resolve complex, congested 1 H NMR spectra with many overlapping spin multiplets, while achieving 50-100 times sensitivity enhancements over conventional thermal counterparts.

Wednesday, January 7, 2015

PhD position in solid-state NMR of nanocatalysts, Lille (France) and Mumbai (India)

From the Ampere Magnetic Resonance List


Dear Colleagues,

A PhD position in solid-state NMR spectroscopy of nanocatalysts is available. It is a joint PhD program between the University of Lille 1 (Lille, France) and TIFR (Mumbai, India). Please forward this email to potential candidates.

Best regards,
Olivier Lafon

Project: NMR Study of Nano-Silica Supported Catalysts

Project PIs: Prof. Olivier Lafon (Universite de Lille 1, France), Dr. Hervé Vezin (CNRS, France) with Indian Collaborators Prof. Vivek Polshettiwar (TIFR, Mumbai) and Prof. P. K. Madhu (TIFR, Mumbai and Hyderabad).

Project Objectives: High surface fibrous nano-silica (KCC-1) are promising materials for numerous applications, including catalysis, medical imaging and drug delivery. The development of tunable synthesis and surface modification process for these nanomaterials require a better understanding of the structure of surface sites and their interactions with various substrates. This project aims at characterizing these sites and interactions via conventional and Dynamic Nuclear Polarization (DNP)-enhanced solid-state NMR. EPR spectroscopy will provide useful information to optimize sample preparation. Structural information thus obtained will be used for a rational improvement of solid base nanocatalysts.

Hosts and research infrastructure: Lille and Mumbai are vibrant cities, imbued with a rich history. Lille is located in the middle of northwestern Europe (only 30 min by high-speed trains from Brussels, 1h from Paris and 1h30 from London). Mumbai lies on the western coast of India by the bank of Arabian Sea. Lille and Mumbai are leading centers for magnetic resonance in their own countries. The project involves research groups internationally known for nanocatalysis, solid-state NMR, DNP and EPR. Vivek Polshettiwar discovered KCC-1 nanomaterials, whereas Olivier Lafon and Herve Vezin pioneered the study of nanostructured materials by DNP-NMR. Lille magnetic resonance facility includes 800 and 900 MHz NMR spectrometers for the study of liquids and solids as well as pulsed EPR spectrometers. It has also been selected recently for the installation of the first 1200 MHz NMR spectrometer in France.

The applicant: We seek application from national and international students who have graduated in physics or chemistry, preferably with a background in material sciences or NMR spectroscopy. The successful applicant will be given the opportunity to work in an exciting environment with national and international collaborations.

Interested candidates may send his/her CV with a covering letter (one single PDF) to Prof. Olivier Lafon by e-mail to olivier.lafon@univ-lille1.fr

Note: Position is available only after receiving the funds from CEFIPRA for this accepted project, which may happen in the next 1 to 3 months.
________________________________________________________________
Olivier Lafon

Department of chemistry
University of Lille North of France
F-59652, Villeneuve d'Ascq, Cedex, France

Tel: 33 3 20 43 41 43 Fax : 33 3 20 43 68 14

________________________________________________________________ 

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Using [1- C]lactic acid for hyperpolarized C MR cardiac studies


Chen, A.P., et al., Using [1- C]lactic acid for hyperpolarized C MR cardiac studies. Magn Reson Med, 2014: p. n/a-n/a.


PURPOSE: Hyperpolarized [1-13 C]lactate in solution may be a clinically relevant and safe substrate for real time MR investigations of key metabolic pathways. The potential of using hyperpolarized [1-13 C]lactate for magnetic resonance studies of cardiac metabolism in vivo was explored. METHODS: Neat [1-13 C]lactic acid was hyperpolarized using the dynamic nuclear polarization process. Cardiac MR spectroscopy experiments were performed in vivo using hyperpolarized [1-13 C]lactate and [1-13 C]pyruvate in solutions. RESULTS: A high degree of polarization was achieved for [1-13 C]lactate in solution (16.7%). 13 C-bicarbonate was observed in rat hearts in vivo after either hyperpolarized [1-13 C]lactate or hyperpolarized [1-13 C]pyruvate was infused, but lower 13 C-bicarbonate to substrate ratio was observed with hyperpolarized [1-13 C]lactate infusions. The response of 13 C-bicarbonate signal as a function of hyperpolarized [1-13 C]lactate doses was also investigated and a saturation of 13 C-bicarbonate signal was observed at the highest dose of [1-13 C]lactate used (0.69 mmol/kg). CONCLUSION: This study demonstrated that the use of neat [1-13 C]lactic acid as the DNP sample is a potential alternative to [1-13 C]pyruvic acid for cardiac hyperpolarized 13 C MR studies. Hyperpolarized [1-13 C]lactate may enable noninvasive assessment of cardiac PDH flux in cardiac patients in the near future. Magn Reson Med, 2014. (c) 2014 Wiley Periodicals, Inc.

Tuesday, January 6, 2015

PhD studentship available at the University of Cambridge, UK (Kevin Brindle Lab)

PhD studentship available at the University of Cambridge, UK (Kevin Brindle Lab):


Monitoring tumour responses to treatment using hyperpolarized magnetic resonance imaging


Kevin M. Brindle
Department of Biochemistry, University of Cambridge
Tennis Court Road, Cambridge CB2 1GA
and
Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre,
Robinson Way, Cambridge, CB2 0RE

Patients with similar tumour types can show markedly different responses to the same therapy. The development of new treatments would benefit, therefore, from the introduction of imaging methods that allow an early assessment of treatment response in individual patients, allowing rapid selection of the most effective treatment [1].

We have been developing methods for detecting the early responses of tumours to therapy, including magnetic resonance (MR) imaging of tumour cell metabolism using hyperpolarized 13C-labelled cellular metabolites. Nuclear spin hyperpolarization can increase sensitivity in the MR experiment by >10,000x. This has allowed us to image the location of labelled cell substrates in vivo and, more importantly, their metabolic conversion into other metabolites. These substrates include pyruvate [2], lactate [3], glutamine [4], glutamate [5], fumarate [6], bicarbonate [7] and ascorbate [8] and glucose [9]. Exchange of hyperpolarized 13C label between lactate and pyruvate can be imaged in models of lymphoma and glioma and this flux is decreased post-treatment [2,10]. Hyperpolarized [1,4-13C]fumarate can be used to detect tumour cell necrosis post treatment in lymphoma [6] and both the polarized pyruvate and fumarate experiments can detect early evidence of treatment response in a breast tumour model [11] and also early responses to anti-vascular [12] and anti-angiogenic drugs [13]. Tissue pH can be imaged from the ratio of the signal intensities of hyperpolarized H13CO3- and 13CO2 following intravenous injection of hyperpolarized H13CO3¯ [7] and tumour redox state can be determined by monitoring the oxidation and reduction of [1-13C]ascorbate and [1-13C]dehydroascorbate respectively [8]. Tumour glycolysis can be monitored by measuring the conversion of hyperpolarized [U-2H, U-13C]glucose to lactate and this flux was shown to decrease post-treatment [9]. 

We have recently obtained funding for clinical trials with polarised pyruvate and fumarate to detect treatment response in lymphoma, glioma and breast cancer patients.

The aim of this studentship is to further develop this technique. This will include investigation of other cell substrates and other ways in which the technique can be used to monitor tumour progression and response to treatment. The student will learn a variety of techniques, including magnetic resonance imaging and spectroscopy; metabolic biochemistry, particularly as it relates to oncology; tumour cell biology and molecular biology.

References


1. Brindle, K., Nature Rev Cancer, 8, 94-107 (2008)
2. Day, S.E., et al., Nature Med, 13, 1382-1387 (2007)
3. Kennedy, B.W.C., et al., J Am Chem Soc, 134, 4969−4977 (2012)
4. Gallagher, F., et al., Magn. Reson. Med., 60, 253-257 (2008)
5. Gallagher, F., et al., Magn Reson Med, 66, 18-23 (2011)
6. Gallagher, F.A., et al., Proc Natl Acad Sci U S A, 106, 19801-19806 (2009)
7. Gallagher, F., et al., Nature, 453, 940-943 (2008)
8. Bohndiek, S.E., et al., J Am Chem Soc, 133, 11795-11801 (2011)
9. Rodrigues, T.B., et al., Nat Med, 20, 93-97 (2014)
10. Day, S.E., et al., Magn Reson Med, 65, 557-563 (2011)
11. Witney, T.H., et al., Brit. J. Cancer, 103, 1400-1406 (2010)
12. Bohndiek, S.E., et al., Molecular Cancer Therapeutics, 9, 3278-3288 (2010)
13. Bohndiek, S.E., et al., Cancer Research, 72, 854-864 (2012)

-- 

Tiago B. Rodrigues, PhD
Phone: +44 (0) 1223 769724
Fax: +44 (0) 1223 769510

CRUK Cambridge Institute,
University of Cambridge,
Li Ka Shing Centre,
Robinson Way,
Cambridge CB2 0RE
United Kingdom

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Monday, January 5, 2015

Let's start the new year with an article that is already a bit older. However, I just came across it recently and I don't think I posted it already. It is a very nice overview about Dissolution DNP by Walther Koeckenberger.

Köckenberger, W., Dissolution Dynamic Nuclear Polarization, in eMagRes. 2007, John Wiley & Sons, Ltd.


Dissolution DNP (dissDNP) is an experimental strategy that can be used to substantially increase the nuclear spin polarization in liquid-state samples. The strategy is based on DNP carried out at cryogenic temperatures with a subsequent fast temperature rise of the sample that is achieved by dissolving the initially frozen sample in a hot solvent. The strategy has opened up novel avenues in medical diagnostic imaging, as 13C-labeled compounds can first be prepared with high-spin polarization by dissDNP before their administration to humans or animals, followed by their in vivo detection using MRI. The use of fast spectroscopic imaging acquisition schemes makes it possible to observe the in vivo spatial distribution of 13C-labeled compounds and monitor their in vivo metabolic turnover due to the high-spin polarization and the related increase in sensitivity. The strategy has also shown to be useful in measuring in vitro metabolism in cell cultures with high time resolution, and in enabling novel experimental protocols for in vitro molecular dynamics studies.