Imaging breast cancer using hyperpolarized carbon-13 MRI.

Abstract:

:Our purpose is to investigate the feasibility of imaging tumor metabolism in breast cancer patients using 13C magnetic resonance spectroscopic imaging (MRSI) of hyperpolarized 13C label exchange between injected [1-13C]pyruvate and the endogenous tumor lactate pool. Treatment-naïve breast cancer patients were recruited: four triple-negative grade 3 cancers; two invasive ductal carcinomas that were estrogen and progesterone receptor-positive (ER/PR+) and HER2/neu-negative (HER2-), one grade 2 and one grade 3; and one grade 2 ER/PR+ HER2- invasive lobular carcinoma (ILC). Dynamic 13C MRSI was performed following injection of hyperpolarized [1-13C]pyruvate. Expression of lactate dehydrogenase A (LDHA), which catalyzes 13C label exchange between pyruvate and lactate, hypoxia-inducible factor-1 (HIF1α), and the monocarboxylate transporters MCT1 and MCT4 were quantified using immunohistochemistry and RNA sequencing. We have demonstrated the feasibility and safety of hyperpolarized 13C MRI in early breast cancer. Both intertumoral and intratumoral heterogeneity of the hyperpolarized pyruvate and lactate signals were observed. The lactate-to-pyruvate signal ratio (LAC/PYR) ranged from 0.021 to 0.473 across the tumor subtypes (mean ± SD: 0.145 ± 0.164), and a lactate signal was observed in all of the grade 3 tumors. The LAC/PYR was significantly correlated with tumor volume (R = 0.903, P = 0.005) and MCT 1 (R = 0.85, P = 0.032) and HIF1α expression (R = 0.83, P = 0.043). Imaging of hyperpolarized [1-13C]pyruvate metabolism in breast cancer is feasible and demonstrated significant intertumoral and intratumoral metabolic heterogeneity, where lactate labeling correlated with MCT1 expression and hypoxia.

authors

Gallagher FA,Woitek R,McLean MA,Gill AB,Manzano Garcia R,Provenzano E,Riemer F,Kaggie J,Chhabra A,Ursprung S,Grist JT,Daniels CJ,Zaccagna F,Laurent MC,Locke M,Hilborne S,Frary A,Torheim T,Boursnell C,Schiller A,Pa

doi

10.1073/pnas.1913841117

subject

Has Abstract

pub_date

2020-01-28 00:00:00

pages

2092-2098

issue

4

eissn

0027-8424

issn

1091-6490

pii

1913841117

journal_volume

117

pub_type

杂志文章
  • Palmitoylation influences the function and pharmacology of sodium channels.

    abstract::Palmitoylation is a common lipid modification known to regulate the functional properties of various proteins and is a vital step in the biosynthesis of voltage-activated sodium (Nav) channels. We discovered a mutation in an intracellular loop of rNav1.2a (G1079C), which results in a higher apparent affinity for exter...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1108497108

    authors: Bosmans F,Milescu M,Swartz KJ

    更新日期:2011-12-13 00:00:00

  • Calcium-dependent copper redistributions in neuronal cells revealed by a fluorescent copper sensor and X-ray fluorescence microscopy.

    abstract::Dynamic fluxes of s-block metals like potassium, sodium, and calcium are of broad importance in cell signaling. In contrast, the concept of mobile transition metals triggered by cell activation remains insufficiently explored, in large part because metals like copper and iron are typically studied as static cellular n...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1009932108

    authors: Dodani SC,Domaille DW,Nam CI,Miller EW,Finney LA,Vogt S,Chang CJ

    更新日期:2011-04-12 00:00:00

  • Receptor-stimulated death pathway is opened by antigen in mature T cells.

    abstract::Clonal deletion provides an important mechanism for the elimination of autoreactive T cells. Deletion is accomplished by programmed cell death directed by interaction of the T-cell receptor (TCR) of the developing thymocyte with major histocompatibility complex elements in the thymic environment. In this report we pre...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.88.6.2151

    authors: Russell JH,White CL,Loh DY,Meleedy-Rey P

    更新日期:1991-03-15 00:00:00

  • Human PEX1 cloned by functional complementation on a CHO cell mutant is responsible for peroxisome-deficient Zellweger syndrome of complementation group I.

    abstract::The peroxisome biogenesis disorders (PBDs), including Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy (NALD), are autosomal recessive diseases caused by defects in peroxisome assembly, for which at least 10 complementation groups have been reported. We have isolated a human PEX1 cDNA (HsPEX1) by functional c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.8.4350

    authors: Tamura S,Okumoto K,Toyama R,Shimozawa N,Tsukamoto T,Suzuki Y,Osumi T,Kondo N,Fujiki Y

    更新日期:1998-04-14 00:00:00

  • Human acetyl-CoA carboxylase 1 gene: presence of three promoters and heterogeneity at the 5'-untranslated mRNA region.

    abstract::Acetyl-CoA carboxylase 1 (ACC1) catalyzes the formation of malonyl-CoA, the C2 donor for de novo synthesis of long-chain fatty acids. We have identified 64 exons, including 7 alternatively spliced minor exons (1A, 1B, 1C, 3, 5A', 5A, and 5B) in human ACC1 gene ( approximately 330 kb). The gene is regulated by three pr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1332670100

    authors: Mao J,Chirala SS,Wakil SJ

    更新日期:2003-06-24 00:00:00

  • Geometric derivation of the chronometric redshift.

    abstract::The chronometric redshift-distance relation z = tan 2(1/2rho), where rho is the distance in radians in the Einstein metric, is derived by an elementary geometric analysis comparable to that in traditional analysis of the expanding universe model. The differential dTt of Einstein time evolution Tt through time t, as ap...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.23.11114

    authors: Segal IE

    更新日期:1993-12-01 00:00:00

  • Climatic shifts drove major contractions in avian latitudinal distributions throughout the Cenozoic.

    abstract::Many higher level avian clades are restricted to Earth's lower latitudes, leading to historical biogeographic reconstructions favoring a Gondwanan origin of crown birds and numerous deep subclades. However, several such "tropical-restricted" clades (TRCs) are represented by stem-lineage fossils well outside the ranges...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1903866116

    authors: Saupe EE,Farnsworth A,Lunt DJ,Sagoo N,Pham KV,Field DJ

    更新日期:2019-06-25 00:00:00

  • Yeast GAL11 protein is a distinctive type transcription factor that enhances basal transcription in vitro.

    abstract::The yeast auxiliary transcription factor GAL11, a candidate for the coactivator, was partially purified from yeast cells, and its function was characterized in a cell-free transcription system. The partially purified GAL11 protein stimulated basal transcription from the CYC1 core promoter by a factor of 4-5 at the ste...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.18.8382

    authors: Sakurai H,Hiraoka Y,Fukasawa T

    更新日期:1993-09-15 00:00:00

  • Visual motion perception.

    abstract::The primate visual motion system performs numerous functions essential for survival in a dynamic visual world. Prominent among these functions is the ability to recover and represent the trajectories of objects in a form that facilitates behavioral responses to those movements. The first step toward this goal, which c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章,评审

    doi:10.1073/pnas.92.7.2433

    authors: Albright TD,Stoner GR

    更新日期:1995-03-28 00:00:00

  • The O-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development.

    abstract::Mechanisms by which the extracellular domain of Notch1 controls Notch1 signaling are not well defined. Here, we show that the O-fucose glycan in the Notch1 ligand-binding domain regulates the strength of Notch1 signaling during embryogenesis, postweaning growth, and T cell development in the mouse. Heterozygotes carry...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0702846105

    authors: Ge C,Stanley P

    更新日期:2008-02-05 00:00:00

  • The endocannabinoid system and pivotal role of the CB2 receptor in mouse spermatogenesis.

    abstract::The exact role of the endocannabinoid system (ECS) during spermatogenesis has not been clarified. We used purified germ cell fractions representative of all phases of spermatogenesis and primary cultures of spermatogonia. This approach allowed the precise quantification of the cannabinoid receptor ligands, anandamide ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0812789106

    authors: Grimaldi P,Orlando P,Di Siena S,Lolicato F,Petrosino S,Bisogno T,Geremia R,De Petrocellis L,Di Marzo V

    更新日期:2009-07-07 00:00:00

  • High-seas fish wars generate marine reserves.

    abstract::The effective management of marine fisheries is an ongoing challenge at the intersection of biology, economics, and policy. One way in which fish stocks-and their habitats-can be protected is through the establishment of marine reserves, areas that are closed to fishing. Although the potential economic benefits of suc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1518509113

    authors: Herrera GE,Moeller HV,Neubert MG

    更新日期:2016-04-05 00:00:00

  • Sodium azide mutagenesis: preferential generation of A.T-->G.C transitions in the barley Ant18 gene.

    abstract::The molecular basis for the absence of anthocyanins and proanthocyanidins in four independent sodium azide-induced ant18 mutants of barley was examined by sequencing the gene encoding dihydroflavonol 4-reductase in these mutants. Sodium azide generated 21 base substitutions, which corresponds to 0.17% of the 12,704 nu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.90.17.8043

    authors: Olsen O,Wang X,von Wettstein D

    更新日期:1993-09-01 00:00:00

  • Thermodynamic prediction of protein neutrality.

    abstract::We present a simple theory that uses thermodynamic parameters to predict the probability that a protein retains the wild-type structure after one or more random amino acid substitutions. Our theory predicts that for large numbers of substitutions the probability that a protein retains its structure will decline expone...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0406744102

    authors: Bloom JD,Silberg JJ,Wilke CO,Drummond DA,Adami C,Arnold FH

    更新日期:2005-01-18 00:00:00

  • Toward a microscopic model of bidirectional synaptic plasticity.

    abstract::We show that a 2-step phospho/dephosphorylation cycle for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid receptor (AMPAR), as used in in vivo learning experiments to assess long-term potentiation (LTP) induction and establishment, exhibits bistability for a wide range of parameters, consistent with val...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905988106

    authors: Castellani GC,Bazzani A,Cooper LN

    更新日期:2009-08-18 00:00:00

  • Comparison of fusion phage libraries displaying VH or single-chain Fv antibody fragments derived from the antibody repertoire of a vaccinated melanoma patient as a source of melanoma-specific targeting molecules.

    abstract::A single-chain Fv (scFv) fusion phage library derived from random combinations of VH and VL (variable heavy and light chains) domains in the antibody repertoire of a vaccinated melanoma patient was previously used to isolate clones that bind specifically to melanoma cells. An unexpected finding was that one of the clo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.94.17.9261

    authors: Cai X,Garen A

    更新日期:1997-08-19 00:00:00

  • Modulation of muscle gene expression in Caenorhabditis elegans: differential levels of transcripts, mRNAs, and polypeptides for thick filament proteins during nematode development.

    abstract::The body-wall muscle cells of the nematode Caenorhabditis elegans produce thick filaments during embryonic, larval, and adult stages. These thick filaments contain two myosin isoforms, A and B, which assemble into different zones along the 10-microns lengths. Paramyosin, a protein homologous to myosin rods, forms a su...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.3.876

    authors: Honda S,Epstein HF

    更新日期:1990-02-01 00:00:00

  • Parkinson's disease-associated iPLA2-VIA/PLA2G6 regulates neuronal functions and α-synuclein stability through membrane remodeling.

    abstract::Mutations in the iPLA2-VIA/PLA2G6 gene are responsible for PARK14-linked Parkinson's disease (PD) with α-synucleinopathy. However, it is unclear how iPLA2-VIA mutations lead to α-synuclein (α-Syn) aggregation and dopaminergic (DA) neurodegeneration. Here, we report that iPLA2-VIA-deficient Drosophila exhibits defects ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1902958116

    authors: Mori A,Hatano T,Inoshita T,Shiba-Fukushima K,Koinuma T,Meng H,Kubo SI,Spratt S,Cui C,Yamashita C,Miki Y,Yamamoto K,Hirabayashi T,Murakami M,Takahashi Y,Shindou H,Nonaka T,Hasegawa M,Okuzumi A,Imai Y,Hattori N

    更新日期:2019-10-08 00:00:00

  • "Real-time" obstacle avoidance in the absence of primary visual cortex.

    abstract::When we reach toward objects, we easily avoid potential obstacles located in the workspace. Previous studies suggest that obstacle avoidance relies on mechanisms in the dorsal visual stream in the posterior parietal cortex. One fundamental question that remains unanswered is where the visual inputs to these dorsal-str...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0905549106

    authors: Striemer CL,Chapman CS,Goodale MA

    更新日期:2009-09-15 00:00:00

  • Abnormal ambient glucose levels inhibit proteoglycan core protein gene expression and reduce proteoglycan accumulation during chondrogenesis: possible mechanism for teratogenic effects of maternal diabetes.

    abstract::Using a tissue culture system based on a nearly pure population of avian precartilage mesenchymal cells, we have found that ambient glucose levels as little as 50% lower, or 100% higher, than normally present in embryonic sera are deleterious to cartilage development, as measured by the accumulation of highly sulfated...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.86.24.10113

    authors: Leonard CM,Bergman M,Frenz DA,Macreery LA,Newman SA

    更新日期:1989-12-01 00:00:00

  • Proteomic identification of phosphatidylinositol (3,4,5) triphosphate-binding proteins in Dictyostelium discoideum.

    abstract::Phosphatidylinositol (3,4,5)-triphosphate (PtdInsP(3)) mediates intracellular signaling for directional sensing and pseudopod extension at the leading edge of migrating cells during chemotaxis. How this PtdInsP(3) signal is translated into remodeling of the actin cytoskeleton is poorly understood. Here, using a proteo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1006153107

    authors: Zhang P,Wang Y,Sesaki H,Iijima M

    更新日期:2010-06-29 00:00:00

  • Critical point for Bose-Einstein condensation of excitons in graphite.

    abstract::An exciton is an electron-hole pair bound by attractive Coulomb interaction. Short-lived excitons have been detected by a variety of experimental probes in numerous contexts. An excitonic insulator, a collective state of such excitons, has been more elusive. Here, thanks to Nernst measurements in pulsed magnetic field...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2012811117

    authors: Wang J,Nie P,Li X,Zuo H,Fauqué B,Zhu Z,Behnia K

    更新日期:2020-12-01 00:00:00

  • Arabidopsis cryptochrome 2 (CRY2) functions by the photoactivation mechanism distinct from the tryptophan (trp) triad-dependent photoreduction.

    abstract::Cryptochromes are blue-light receptors mediating various light responses in plants and animals. The photochemical mechanism of cryptochromes is not well understood. It has been proposed that photoactivation of cryptochromes involves the blue-light-dependent photoreduction of flavin adenine dinucleotide via the electro...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1114579108

    authors: Li X,Wang Q,Yu X,Liu H,Yang H,Zhao C,Liu X,Tan C,Klejnot J,Zhong D,Lin C

    更新日期:2011-12-20 00:00:00

  • The chondrogenic transcription factor Sox9 is a target of signaling by the parathyroid hormone-related peptide in the growth plate of endochondral bones.

    abstract::In the growth plate of endochondral bones, parathyroid hormone (PTH)-related peptide (PTHrP) regulates the rate of chondrocyte maturation from prehypertrophic chondrocytes to hypertrophic chondrocytes. Using an antibody specific for Sox9 phosphorylated at serine 181 (S(181)), one of the two consensus protein kinase A ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.011393998

    authors: Huang W,Chung UI,Kronenberg HM,de Crombrugghe B

    更新日期:2001-01-02 00:00:00

  • Defective G protein activation of the cAMP pathway in rat kidney during genetic hypertension.

    abstract::The development of hypertension in the spontaneously hypertensive rat (SHR) is associated with renal dysfunction and vasoconstriction. The kidneys of young SHRs exhibit exaggerated reactivity to angiotensin II (Ang-II) and attenuated responses to vasodilators that normally activate the cAMP signal to buffer hormone-in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.92.7.2924

    authors: Chatziantoniou C,Ruan X,Arendshorst WJ

    更新日期:1995-03-28 00:00:00

  • Frequency modulation of neural oscillations according to visual task demands.

    abstract::Temporal integration in visual perception is thought to occur within cycles of occipital alpha-band (8-12 Hz) oscillations. Successive stimuli may be integrated when they fall within the same alpha cycle and segregated for different alpha cycles. Consequently, the speed of alpha oscillations correlates with the tempor...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1713318115

    authors: Wutz A,Melcher D,Samaha J

    更新日期:2018-02-06 00:00:00

  • Conformational transitions in DNA polymerase I revealed by single-molecule FRET.

    abstract::The remarkable fidelity of most DNA polymerases depends on a series of early steps in the reaction pathway which allow the selection of the correct nucleotide substrate, while excluding all incorrect ones, before the enzyme is committed to the chemical step of nucleotide incorporation. The conformational transitions t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0910909107

    authors: Santoso Y,Joyce CM,Potapova O,Le Reste L,Hohlbein J,Torella JP,Grindley ND,Kapanidis AN

    更新日期:2010-01-12 00:00:00

  • On the primary nature of fluorescence yield changes associated with photosynthesis.

    abstract::Absorbance changes of C-550 and cytochrome b(559), and fluorescence-yield changes were measured during irradiation of chloroplasts at -196 degrees . The photo-reduction of C-550 proceeded more rapidly than the photo-oxidation of cytochrome b(559), and the fluorescence-yield change had similar kinetics to the cytochrom...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.11.3420

    authors: Butler WL

    更新日期:1972-11-01 00:00:00

  • Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins.

    abstract::Two high molecular weight heat shock proteins, HSP90 (Mr, 90,000) and HSP100 (Mr, 100,000), were separately purified from extracts of cultured cells of a mouse lymphoma cell line, L5178Y. Both of the HSPs exist in homodimeric form under physiological conditions. Their physicochemical properties are quite similar to ea...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.21.8054

    authors: Koyasu S,Nishida E,Kadowaki T,Matsuzaki F,Iida K,Harada F,Kasuga M,Sakai H,Yahara I

    更新日期:1986-11-01 00:00:00

  • Effects of environmental stressors on daily governance.

    abstract::Human workers ensure the functioning of governments around the world. The efficacy of human workers, in turn, is linked to the climatic conditions they face. Here we show that the same weather that amplifies human health hazards also reduces street-level government workers' oversight of these hazards. To do so, we emp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1803765115

    authors: Obradovich N,Tingley D,Rahwan I

    更新日期:2018-08-28 00:00:00