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23-11-2022 | Positron Emission Tomography | Research Article

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

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

Published in: Molecular Imaging and Biology | Issue 2/2023

Abstract

Introduction

The reliance on glycolytic metabolism is a hallmark of tumor metabolism. Excess acid and protons are produced, leading to an acidic tumor environment. Therefore, we explored the relationship between the tumor glycolytic metabolism and tissue pH by comparing ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET) and hyperpolarized [1-¹³C]pyruvate MR spectroscopy imaging (MRSI) to chemical exchange saturation transfer (CEST) MRI measurements of tumor pH.

Methods

10⁶ C6 glioma cells were implanted in the brains of male Wistar rats (N = 11) using stereotactic surgery. A 60-min PET acquisition after a bolus of FDG was performed at 11–13 days post implantation, and standardized uptake value (SUV) was calculated. CEST measurements were acquired the following day before and during constant infusion of glucose solution. Tumor intracellular pH (pHi) was evaluated using amine and amide concentration-independent detection (AACID) CEST MRI. The change of pH_i (∆pH_i) was calculated as the difference between pH_i pre- and during glucose infusion. Rats were imaged immediately with hyperpolarized [1-¹³C]pyruvate MRSI. Regional maps of the ratio of Lac:Pyr were acquired. The correlations between SUV, Lac:Pyr ratio, and ∆pH_i were evaluated using Pearson’s correlation.

Results

A decrease of 0.14 in pH_i was found after glucose infusion in tumor region. Significant correlations between tumor glycolysis measurements of Lac:Pyr and ∆pH_i within the tumor (ρ = 0.83, P = 0.01) and peritumoral region (ρ = 0.76, P = 0.028) were observed. No significant correlations were found between tumor SUV and ∆pH_i within the tumor (ρ = − 0.45, P = 0.17) and peritumor regions (ρ = − 0.6, P = 0.051).

Conclusion

AACID detected the changes in pH_i induced by glucose infusion. Significant correlations between tumor glycolytic measurement of Lac:Pyr and tumoral and peritumoral pH_i and ∆pH_i suggest the intrinsic relationship between tumor glycolytic metabolism and the tumor pH environment as well as the peritumor pH environment.

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Title: Glucose Infusion Induced Change in Intracellular pH and Its Relationship with Tumor Glycolysis in a C6 Rat Model of Glioblastoma
Authors: Qi Qi
Matthew S. Fox
Heeseung Lim
Rebecca Sullivan
Alex Li
Miranda Bellyou
Lise Desjardins
Andrew McClennan
Robert Bartha
Lisa Hoffman
Timothy J. Scholl
Ting-Yim Lee
Jonathan D. Thiessen
Publication date: 23-11-2022
Publisher: Springer International Publishing
Keyword: Positron Emission Tomography
Published in: Molecular Imaging and Biology / Issue 2/2023
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-022-01726-0

Keynote webinar | Spotlight on medication adherence

Springer Medicine

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

Abstract

Introduction

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

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