Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

Polvoy, Ilona; Qin, Hecong; Flavell, Robert R.; Gordon, Jeremy W.; Viswanath, Pavithra; Sriram, Renuka; Ohliger, Michael A.; Wilson, David M.

doi:10.3390/metabo11090570

Cited by 20 publications

(21 citation statements)

References 132 publications

(161 reference statements)

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“…Unfortunately, this method has been technically challenging to implement in clinical settings. Deuterium-labeled isotopes offer an alternative for metabolic imaging in vivo 13,14 . For example, deuterium metabolic imaging (DMI) was used to map differential metabolism of glucose within aggressive glioblastoma multiforme lesions compared to surrounding brain parenchyma 15 .…”

Section: Introductionmentioning

confidence: 99%

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

Brender

Assmann

Farthing

et al. 2023

Preprint

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In vivo deuterated water (2H2O) labeling leads to deuterium (2H) incorporation into biomolecules of proliferating cells and provides the basis for its use in cell kinetics research. We hypothesized that rapidly proliferating cancer cells would become preferentially labeled with 2H and, therefore, could be visualized by deuterium magnetic resonance imaging (dMRI) following a brief period of in vivo systemic 2H2O administration. We initiated systemic 2H2O administration in two xenograft mouse models harboring either human colorectal, HT-29, or pancreatic, MiaPaCa-2, tumors and 2H2O level of ~ 8% in total body water (TBW). Three schemas of 2H2O administration were tested: 1) starting at tumor seeding and continuing for 7 days of in vivo growth with imaging on day 7, 2) starting at tumor seeding and continuing for 14 days of in vivo growth with imaging on day 14, and 3) initiation of labeling following a week of in vivo tumor growth and continuing until imaging was performed on day 14. Deuterium chemical shift imaging of the tumor bearing limb and contralateral control was performed on either day 7 of 14 after tumor seeding, as described. After 14 days of in vivo tumor growth and 7 days of systemic labeling with 2H2O, a clear deuterium contrast was demonstrated between the xenografts and normal tissue. Labeling in the second week after tumor implantation afforded the highest contrast between neoplastic and healthy tissue in both models. Systemic labeling with 2H2O can be used to create imaging contrast between tumor and healthy issue, providing a non-radioactive method for in vivo cancer imaging.

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Section: Introductionmentioning

confidence: 99%

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

Brender

Assmann

Farthing

et al. 2023

Preprint

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“…[4][5][6][7][8] However, information regarding downstream metabolic processes, which is of fundamental importance for tumor detection and evaluation of therapeutic treatment, cannot be obtained by FDG-PET. Hyperpolarized 13 C MRI shows the capability of interrogating tumor metabolism, but is limited to molecules with long T 1 relaxation times on the 13 C nuclei. 9,10 Biologically important molecules, such as fructose and glucose, which are the main sources of energy in HCC, 11 have short 13 C T 1 lifetimes and thus remain challenging for applications in a clinical setting.…”

Section: Introductionmentioning

confidence: 99%

[6,6′‐²H₂] fructose as a deuterium metabolic imaging probe in liver cancer

et al. 2023

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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer‐related deaths. Imaging plays a crucial role in the early detection of HCC, although current methods are limited in their ability to characterize liver lesions. Most recently, deuterium metabolic imaging (DMI) has been demonstrated as a powerful technique for the imaging of metabolism in vivo. Here, we assess the metabolic flux of [6,6′‐2H2] fructose in cell cultures and in subcutaneous mouse models at 9.4 T. We compare these rates with the most widely used DMI probe, [6,6′‐2H2] glucose, exploring the possibility of developing 2H fructose to overcome the limitations of glucose as a novel DMI probe for detecting liver tumors. Comparison of the in vitro metabolic rates implies their similar glycolytic metabolism in the TCA cycle due to comparable production rates of 2H glutamate/glutamine (glx) for the two precursors, but overall higher glycolytic metabolism from 2H glucose because of a higher production rate of 2H lactate. In vivo kinetic studies suggest that HDO can serve as a robust reporter for the consumption of the precursors in liver tumors. As fructose is predominantly metabolized in the liver, deuterated water (HDO) produced from 2H fructose is probably less contaminated from whole‐body metabolism in comparison with glucose. Moreover, in studies of the normal liver, 2H fructose is readily converted to 2H glx, enabling the characterization of 2H fructose kinetics. This overcomes a major limitation of previous 2H glucose studies in the liver, which were unable to confidently discern metabolic flux due to overlapped signals of 2H glucose and its metabolic product, 2H glycogen. This suggests a unique role for 2H fructose metabolism in HCC and the normal liver, making it a useful approach for assessing liver‐related diseases and the progression to oncogenesis.

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“…This emerging technique has great potential in characterizing the energy metabolism in the brain, 6 liver, 11 and heart, 12 quantifying the glycolytic flux 13 or choline uptake, 14 and monitoring the tumor cell death in cancerous tissues 15 . Unlike PET, 2 H‐MRSI can provide information about the tricarboxylic acid (TCA) cycle and glycolytic metabolism information in addition to glucose uptake 16 . Besides, 2 H‐MRS uses stable nonradioactive isotopes, allowing signal detection over a more flexible time window, and 2 H signal detected from the water in natural abundance could be used as an internal reference to further quantify the concentration of other 2 H‐labeled metabolites.…”

Section: Introductionmentioning

confidence: 99%

A new deuterium‐labeled compound [2,3,4,6,6’‐²H₅]‐D‐glucose for deuterium magnetic resonance metabolic imaging

Zou

Ruan

et al. 2022

NMR in Biomedicine

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Deuterium ( 2 H) magnetic resonance imaging is an emerging approach for noninvasively studying glucose metabolism in vivo, which is important for understanding pathogenesis and monitoring the progression of many diseases such as tumors, diabetes, and neurodegenerative diseases. However, the synthesis of 2 H-labeled glucose is costly because of the expensive raw substrates and the requirement for extreme reaction conditions, making the 2 H-labeled glucose rather expensive and unaffordable for clinic use. In this study, we present a new deuterated compound, [2,3,4,6,6'-2 H 5 ]-D-glucose, with an approximate 10-fold reduction in production costs. The synthesis route uses cheaper raw substrate methyl-α-D-glucopyranoside, relies on mild reaction conditions (80 C), and has higher deuterium labeling efficiency. Magnetic resonance spectroscopy (MRS) and mass spectroscopy experiments confirmed the successful deuterium labeling in the compound. Animal studies demonstrated that the substrate could describe the glycolytic metabolism in a glioma rat model by quantifying the downstream metabolites through 2 H-MRS on an ultrahigh field system. Comparison of the glucose metabolism characteristics was carried out between [2,3,4,6,6'-2 H 5 ]-D-glucose and commercial [6,6'-2 H 2 ]-Dglucose in the animal studies. This cost-effective compound will help facilitate the clinical translation of deuterium magnetic resonance imaging, and enable this powerful metabolic imaging modality to be widely used in both preclinical and clinical research and applications.

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Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

Cited by 20 publications

References 132 publications

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

[6,6′‐²H₂] fructose as a deuterium metabolic imaging probe in liver cancer

A new deuterium‐labeled compound [2,3,4,6,6’‐²H₅]‐D‐glucose for deuterium magnetic resonance metabolic imaging

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Deuterium Metabolic Imaging—Rediscovery of a Spectroscopic Tool

Cited by 20 publications

References 132 publications

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

In vivo deuterium magnetic resonance imaging of xenografted tumors following systemic administration of deuterated water

[6,6′‐2H2] fructose as a deuterium metabolic imaging probe in liver cancer

A new deuterium‐labeled compound [2,3,4,6,6’‐2H5]‐D‐glucose for deuterium magnetic resonance metabolic imaging

Contact Info

Product

Resources

About

[6,6′‐²H₂] fructose as a deuterium metabolic imaging probe in liver cancer

A new deuterium‐labeled compound [2,3,4,6,6’‐²H₅]‐D‐glucose for deuterium magnetic resonance metabolic imaging