Glucose Infusion Induced Change in Intracellular pH and Its Relationship with Tumor Glycolysis in a C6 Rat Model of Glioblastoma

Qi, Qi; Fox, Matthew S.; Lim, Heeseung; Sullivan, Rebecca; Li, Alex; Bellyou, Miranda; Desjardins, Lise; McClennan, Andrew; Bartha, Robert; Hoffman, Lisa; Scholl, Timothy J.; Lee, Ting‐Yim; Thiessen, Jonathan D.

doi:10.1007/s11307-022-01726-0

Cited by 7 publications

(16 citation statements)

References 26 publications

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“… 34 The pH i (Figure 1I) was calculated from the linear dependence between pH i and the AACID ratio, according to Equation (2). 34,65 A T 1 ‐weighted MR image (Figure 1J) was used to localize and define a region of interest (ROI) for the tumor (indicated with a black contour in Figure 1) and delineate the entire brain (indicated with a blue contour in Figure 1). A second ROI corresponding to normal brain tissue (indicated with a green contour in Figure 1) was defined in the contralateral brain hemisphere for comparisons with tumor measurements.…”

Section: Resultsmentioning

confidence: 99%

“…The pH i was calculated from the AACID ratio assuming a linear dependence according to:

{pH}_{i} goodbreak= m \cdot italicAACID goodbreak+ c,

where m = −1.42 and c = 11.61 65 …”

Section: Methodsmentioning

confidence: 99%

“…where m = À1.42 and c = 11.61. 65 The pH e was calculated in each MRSI voxel from the 1 H chemical shifts δ 2 , δ 3 , and δ 6 of H2, H3, and H6 protons of TmDOTP 5À , respectively, as previously described. 40,41,50 Briefly, a multiparametric second-order polynomial equation was used to describe the relationship between pH e and TmDOTP 5À chemical shifts:…”

Section: Mri and Mrsi Data Processingmentioning

confidence: 99%

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Transmembrane pH gradient imaging in rodent glioma models

Mishra,

Santana,

Mihailovic

et al. 2024

NMR in Biomedicine

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A unique feature of the tumor microenvironment is extracellular acidosis in relation to intracellular milieu. Metabolic reprogramming in tumors results in overproduction of H+ ions (and lactate), which are extruded from the cells to support tumor survival and progression. As a result, the transmembrane pH gradient (ΔpH), representing the difference between intracellular pH (pHi) and extracellular pH (pHe), is posited to be larger in tumors compared with normal tissue. Controlling the transmembrane pH difference has promise as a potential therapeutic target in cancer as it plays an important role in regulating drug delivery into cells. The current study shows successful development of an MRI/MRSI‐based technique that provides ΔpH imaging at submillimeter resolution. We applied this technique to image ΔpH in rat brains with RG2 and U87 gliomas, as well as in mouse brains with GL261 gliomas. pHi was measured with Amine and Amide Concentration‐Independent Detection (AACID), while pHe was measured with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). The results indicate that pHi was slightly higher in tumors (7.40–7.43 in rats, 7.39–7.47 in mice) compared with normal brain (7.30–7.38 in rats, 7.32–7.36 in mice), while pHe was significantly lower in tumors (6.62–6.76 in rats, 6.74–6.84 in mice) compared with normal tissue (7.17–7.22 in rats, 7.20–7.21 in mice). As a result, ΔpH was higher in tumors (0.64–0.81 in rats, 0.62–0.65 in mice) compared with normal brain (0.13–0.16 in rats, 0.13–0.16 in mice). This work establishes an MRI/MRSI‐based platform for ΔpH imaging at submillimeter resolution in gliomas.

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Section: Resultsmentioning

confidence: 99%

“…The pH i was calculated from the AACID ratio assuming a linear dependence according to:

{pH}_{i} goodbreak= m \cdot italicAACID goodbreak+ c,

where m = −1.42 and c = 11.61 65 …”

Section: Methodsmentioning

confidence: 99%

Section: Mri and Mrsi Data Processingmentioning

confidence: 99%

See 1 more Smart Citation

Transmembrane pH gradient imaging in rodent glioma models

Mishra,

Santana,

Mihailovic

et al. 2024

NMR in Biomedicine

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show abstract

“…In this regard, carbonic anhydrase (CA) enzyme has influential role to control the kinetics and location of the pH changes [8]. The pulmonary and the renal are the two main systems that modulate pH using carbon dioxide and bicarbonate, respectively [8,[52][53][54]. In former case, the projection of CO2 is utilized to adjust the body's pH, but in latter case, the pH is regularized through a complex system of nephrons that enable bicarbonate to be reabsorbed and or excreted in urination process.…”

Section: Ph Regulation In Human Bodymentioning

confidence: 99%

pH Monitoring in Biological Environment: An Overview of Conventional to Cutting-Edge Sensing Platforms

Akhtar¹,

Nawaz²,

Liu³

et al. 2023

Preprint

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pH is considered one of the paramount factors in bodily functions, because most of the cellular tasks exclusively rely on precise pH values. The regulation of pH is a necessary feature of the intracellular atmosphere and can be established as a strong indicator to judge a physiological abnormality in most of the cases. In this context, the current techniques for pH sensing provide us with the futuristic insight to further design therapeutic and diagnostic tools. Thus, pH-sensing (electrochemically and optically) is rapidly evolving toward exciting new applications and expanding researchers’ interests in many chemical contexts, especially in biomedical applications. The adaptation of cutting-edge technology is subsequently producing the modest form of these biosensors as wearable devices, which are providing us the opportunity to target the real-time collection of vital parameters, including pH for improved healthcare systems. The motif of this review is to provide an insight of trending tech-based systems employed in real time or in-vivo pH responsive monitoring. Herein, we briefly go through the pH regulation in the human body to help the beginners and scientific community with quick background knowledge, recent advances in the field, and pH detection in cancerous environments. In the end, we summarize our review by providing an outlook; challenges that need to be addressed and prospective integration of various pH in vivo platforms with modern electronics that can open new avenues of cutting-edge techniques for disease diagnostics and prevention.

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“…Therefore, after the injection of HP [1-13C] pyruvate, rapid 13C MR was used to measure the metabolic conversion of this aggressive cancer and its response to treatment, with direct biological significance ( Fantin et al, 2006 ; Keshari et al, 2013a ; Keshari et al, 2013b ; Wilson and Kurhanewicz, 2014 ). Using this approach, Qi et al (2022) utilized 18F-FDG-PET and HP [1-13C]pyruvate MRSI with chemical exchange saturation transfer (CEST) MRI measures to investigate the effect of glucose infusion on intracellular pH and its relationship to the tumor.…”

Section: Introductionmentioning

confidence: 99%

Imaging glucose metabolism to reveal tumor progression

Meng

Sun²,

Zhang³

et al. 2023

Front. Physiol.

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Purpose: To analyze and review the progress of glucose metabolism-based molecular imaging in detecting tumors to guide clinicians for new management strategies.Summary: When metabolic abnormalities occur, termed the Warburg effect, it simultaneously enables excessive cell proliferation and inhibits cell apoptosis. Molecular imaging technology combines molecular biology and cell probe technology to visualize, characterize, and quantify processes at cellular and subcellular levels in vivo. Modern instruments, including molecular biochemistry, data processing, nanotechnology, and image processing, use molecular probes to perform real-time, non-invasive imaging of molecular and cellular events in living organisms.Conclusion: Molecular imaging is a non-invasive method for live detection, dynamic observation, and quantitative assessment of tumor glucose metabolism. It enables in-depth examination of the connection between the tumor microenvironment and tumor growth, providing a reliable assessment technique for scientific and clinical research. This new technique will facilitate the translation of fundamental research into clinical practice.

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Glucose Infusion Induced Change in Intracellular pH and Its Relationship with Tumor Glycolysis in a C6 Rat Model of Glioblastoma

Cited by 7 publications

References 26 publications

Transmembrane pH gradient imaging in rodent glioma models

Transmembrane pH gradient imaging in rodent glioma models

pH Monitoring in Biological Environment: An Overview of Conventional to Cutting-Edge Sensing Platforms

Imaging glucose metabolism to reveal tumor progression

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