Related ArticlesCombining Hyperpolarized Real-Time Metabolic Imaging and NMR Spectroscopy To Identify Metabolic Biomarkers in Pancreatic Cancer.
J Proteome Res. 2019 07 05;18(7):2826-2834
Authors: Dutta P, Perez MR, Lee J, Kang Y, Pratt M, Salzillo TC, Weygand J, Zacharias NM, Gammon ST, Koay EJ, Kim M, McAllister F, Sen S, Maitra A, Piwnica-Worms D, Fleming JB, Bhattacharya PK
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that progresses without any symptom, and oftentimes, it is detected at an advanced stage. The lack of prior symptoms and effective treatments have created a knowledge gap in the management of this lethal disease. This issue can be addressed by developing novel noninvasive imaging-based biomarkers in PDAC. We explored in vivo hyperpolarized (HP) 13C MRS of pyruvate to lactate conversion and ex vivo 1H NMR spectroscopy in a panel of well-annotated patient-derived PDAC xenograft (PDXs) model and investigated the correlation between aberrant glycolytic metabolism and aggressiveness of the tumor. Real-time metabolic imaging data demonstrate the immediate intracellular conversion of HP 13C pyruvate to lactate after intravenous injection interrogating upregulated lactate dehydrogenase (LDH) activity in aggressive PDXs. Total ex vivo lactate measurement by 1H NMR spectroscopy showed a direct correlation with in vivo dynamic pyruvate-to-lactate conversion and demonstrated the potential of dynamic metabolic flux as a biomarker of total lactate concentration and aggressiveness of the tumor. Furthermore, the metabolite concentrations were very distinct among all four tumor types analyzed in this study. Overexpression of LDH-A and hypoxia-inducible factor (HIF-1?) plays a significant role in the conversion kinetics of HP pyruvate-to-lactate in tumors. Collectively, these data identified aberrant metabolic characteristics of pancreatic cancer PDXs and could potentially delineate metabolic targets for therapeutic intervention. Metabolic imaging with HP pyruvate and NMR metabolomics may enable identification and classification of aggressive subtypes of patient-derived xenografts. Translation of this real-time metabolic technique to the clinic may have the potential to improve the management of patients at high risk of developing pancreatic diseases.
High-resolution hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE
From The DNP-NMR Blog:
High-resolution hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE
Wespi, P., et al., High-resolution hyperpolarized metabolic imaging of the rat heart using k-t PCA and k-t SPARSE. NMR Biomed, 2018. 31(2): p. e3876-n/a.
https://www.ncbi.nlm.nih.gov/pubmed/29244228
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02-26-2018 04:18 PM
[NMR paper] Impact of chemotherapy on metabolic reprogramming: Characterization of the metabolic profile of breast cancer MDA-MB-231 cells using (1)H HR-MAS NMR spectroscopy.
Impact of chemotherapy on metabolic reprogramming: Characterization of the metabolic profile of breast cancer MDA-MB-231 cells using (1)H HR-MAS NMR spectroscopy.
Related Articles Impact of chemotherapy on metabolic reprogramming: Characterization of the metabolic profile of breast cancer MDA-MB-231 cells using (1)H HR-MAS NMR spectroscopy.
J Pharm Biomed Anal. 2017 Sep 12;146:324-328
Authors: Maria RM, Altei WF, Selistre-de-Araujo HS, Colnago LA
Abstract
Doxorubicin, cisplatin, and tamoxifen are part of many chemotherapeutic...
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09-16-2017 09:58 PM
Hyperpolarized [1,4-(13)C]-diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging
From The DNP-NMR Blog:
Hyperpolarized -diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging
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Billingsley, K.L., et al., Hyperpolarized -diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging. NMR Biomed, 2014. 27(3): p. 356-62.
https://www.ncbi.nlm.nih.gov/pubmed/24421249
Metabolic imaging of patients with prostate cancer using hyperpolarized [1-(1)(3)C]pyruvate
From The DNP-NMR Blog:
Metabolic imaging of patients with prostate cancer using hyperpolarized pyruvate
Nelson, S.J., et al., Metabolic imaging of patients with prostate cancer using hyperpolarized pyruvate. Sci Transl Med, 2013. 5(198): p. 198ra108.
http://www.ncbi.nlm.nih.gov/pubmed/23946197
Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging
From The DNP-NMR Blog:
Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging
Eichhorn, T.R., et al., Hyperpolarization without persistent radicals for in vivo real-time metabolic imaging. Proc. Nat. Aca. Sci. USA, 2013. 110(45): p. 18064-18069.
http://www.pnas.org/content/110/45/18064.abstract
Combining Hyperpolarized Real-Time Metabolic Imaging and NMR Spectroscopy To Identify Metabolic Biomarkers in Pancreatic Cancer.
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