(13) C magnetic resonance spectroscopy measurements with hyperpolarized [1-(13) C] pyruvate can be used to detect the expression of transgenic pyruvate decarboxylase activity in vivo.
Magnetic Resonance in Medicine 76(2):391 (2016)
Dissolution dynamic nuclear polarization can increase the sensitivity of the (13) C magnetic resonance spectroscopy experiment by at least four orders of magnitude and offers a novel approach to the development of MRI gene reporters based on enzymes that metabolize (13) C-labeled tracers. We des...
Effects of fasting on serial measurements of hyperpolarized [1-(13) C]pyruvate metabolism in tumors.
NMR in Biomedicine 29(8):1048 (2016)
Imaging of the metabolism of hyperpolarized [1-(13) C]pyruvate has shown considerable promise in preclinical studies in oncology, particularly for the assessment of early treatment response. The repeatability of measurements of (13) C label exchange between pyruvate and lactate was determined in...
Development of Timd2 as a reporter gene for MRI.
Magnetic Resonance in Medicine 75(4):1697 (2016)
To assess the potential of an MRI gene reporter based on the ferritin receptor Timd2 (T-cell immunoglobulin and mucin domain containing protein 2), using T1- and T2-weighted imaging.
Pellets of cells that had been modified to express the Timd2 transgene, and incubated with either iron-loaded or ...
MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model.
Gut 65(3):465 (2016)
Pancreatic cancer (PCa) is treatable by surgery when detected at an early stage. Non-invasive imaging methods able to detect both established tumours and their precursor lesions are needed to select patients for surgery. We investigated here whether pancreatic preneoplasia could be detected prio...
Imaging Glycosylation In Vivo by Metabolic Labeling and Magnetic Resonance Imaging.
Angewandte Chemie. International edition in Eng... 55(4):1286 (2016)
Glycosylation is a ubiquitous post-translational modification, present in over 50% of the proteins in the human genome, with important roles in cell-cell communication and migration. Interest in glycome profiling has increased with the realization that glycans can be used as biomarkers of many d...
Hyperpolarized [U-(2) H, U-(13) C]Glucose reports on glycolytic and pentose phosphate pathway activity in EL4 tumors and glycolytic activity in yeast cells.
Magnetic Resonance in Medicine 74(6):1543 (2015)
A resonance at ∼181 ppm in the (13) C spectra of tumors injected with hyperpolarized [U-(2) H, U-(13) C]glucose was assigned to 6-phosphogluconate (6PG), as in previous studies in yeast, whereas in breast cancer cells in vitro this resonance was assigned to 3-phosphoglycerate (3PG). These peak a...
Carbonic Anhydrase Activity Monitored In Vivo by Hyperpolarized 13C-Magnetic Resonance Spectroscopy Demonstrates Its Importance for pH Regulation in Tumors.
Cancer Research 75(19):4109 (2015)
Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3 (-)). We assessed the functional activity of CAIX in two colorectal tumor models, expressing different levels of the enzyme, by measuring the rate of exchange of hyperpolari...
(13) C magnetic resonance spectroscopic imaging of hyperpolarized [1-(13) C, U-(2) H5 ] ethanol oxidation can be used to assess aldehyde dehydrogenase activity in vivo.
Magnetic Resonance in Medicine 73(5):1733 (2015)
Aldehyde dehydrogenase (ALDH2) is an emerging drug target for the treatment of heart disease, cocaine and alcohol dependence, and conditions caused by genetic polymorphisms in ALDH2. Noninvasive measurement of ALDH2 activity in vivo could inform the development of these drugs and accelerate thei...
Detection of transgene expression using hyperpolarized 13C urea and diffusion-weighted magnetic resonance spectroscopy.
Magnetic Resonance in Medicine 73(4):1401 (2015)
To assess the potential of a gene reporter system, based on a urea transporter (UTB) and hyperpolarized [(13) C]urea.
Mice were implanted subcutaneously with either unmodified control cells or otherwise identical cells expressing UTB. After injection of hyperpolarized [(13) C]urea, a spin echo s...
Amplification of TRIM44: pairing a prognostic target with potential therapeutic strategy.
JNCI Journal of the National Cancer Institute 106(5) (2014)
Many prognostic biomarkers have been proposed recently. However, there is a lack of therapeutic strategies exploiting novel prognostic biomarkers. We aimed to propose therapeutic options in patients with overexpression of TRIM44, a recently identified prognostic gene.
Genomic and transcriptomic ...
In vivo single-shot 13C spectroscopic imaging of hyperpolarized metabolites by spatiotemporal encoding.
Hyperpolarized metabolic imaging is a growing field that has provided a new tool for analyzing metabolism, particularly in cancer. Given the short life times of the hyperpolarized signal, fast and effective spectroscopic imaging methods compatible with dynamic metabolic characterizations are nec...
Dual-modality gene reporter for in vivo imaging.
PNAS 111(1):415 (2014)
The ability to track cells and their patterns of gene expression in living organisms can increase our understanding of tissue development and disease. Gene reporters for bioluminescence, fluorescence, radionuclide, and magnetic resonance imaging (MRI) have been described but these suffer various...
Quantitation of a spin polarization-induced nuclear Overhauser effect (SPINOE) between a hyperpolarized (13) C-labeled cell metabolite and water protons.
Contrast Media and Molecular Imaging 9(2):182 (2014)
The spin polarization-induced nuclear Overhauser effect (SPINOE) describes the enhancement of spin polarization of solvent nuclei by the hyperpolarized spins of a solute. In this communication we demonstrate that SPINOEs can be observed between [1,4-(13) C2 ]fumarate, hyperpolarized using the di...
Analysis of image heterogeneity using 2D Minkowski functionals detects tumor responses to treatment.
Magnetic Resonance in Medicine 71(1):402 (2014)
The acquisition of ever increasing volumes of high resolution magnetic resonance imaging (MRI) data has created an urgent need to develop automated and objective image analysis algorithms that can assist in determining tumor margins, diagnosing tumor stage, and detecting treatment response.
Magnetic resonance imaging of tumor glycolysis using hyperpolarized 13C-labeled glucose.
Nature Medicine 20(1):93 (2014)
In this study, we monitored glycolysis in mouse lymphoma and lung tumors by measuring the conversion of hyperpolarized [U-2H, U-13C]glucose to lactate using 13C magnetic resonance spectroscopy and spectroscopic imaging. We observed labeled lactate only in tumors and not in surrounding normal tis...
Hyperpolarized singlet lifetimes of pyruvate in human blood and in the mouse.
NMR in Biomedicine 26(12):1696 (2013)
Hyperpolarized NMR is a promising technique for non-invasive imaging of tissue metabolism in vivo. However, the pathways that can be studied are limited by the fast T1 decay of the nuclear spin order. In metabolites containing pairs of coupled nuclear spins-1/2, the spin order may be maintained ...
Spin echo measurements of the extravasation and tumor cell uptake of hyperpolarized [1-(13) C]lactate and [1-(13) C]pyruvate.
Magnetic Resonance in Medicine 70(5):1200 (2013)
To assess the blood-tissue distribution of hyperpolarized (13) C-labeled molecules in vivo.
Spin-echo experiments with simultaneous acquisition of the free induction decay (FID) signal following the excitation pulse and the spin-echo signal, were used to monitor hyperpolarized [1-(13) C]lactate,...
Magnetic resonance imaging with hyperpolarized [1,4-(13)C2]fumarate allows detection of early renal acute tubular necrosis.
PNAS 109(33):13374 (2012)
Acute kidney injury (AKI) is a common and important medical problem, affecting 10% of hospitalized patients, and it is associated with significant morbidity and mortality. The most frequent cause of AKI is acute tubular necrosis (ATN). Current imaging techniques and biomarkers do not allow ATN t...
Direct enhancement of nuclear singlet order by dynamic nuclear polarization.
Journal of the American Chemical Society 134(18):7668 (2012)
Hyperpolarized singlet order is available immediately after dissolution DNP, avoiding need for additional preparation steps. We demonstrate this procedure on a sample of [1,2-(13)C(2)]pyruvic acid.
Probing lactate dehydrogenase activity in tumors by measuring hydrogen/deuterium exchange in hyperpolarized l-[1-(13)C,U-(2)H]lactate.
Journal of the American Chemical Society 134(10):4969 (2012)
(13)C magnetic resonance spectroscopy and spectroscopic imaging measurements of hyperpolarized (13)C label exchange between exogenously administered [1-(13)C]pyruvate and endogenous lactate, catalyzed by lactate dehydrogenase (LDH), has proved to be a powerful approach for probing tissue metabol...