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Preliminary Results that Assess Metformin Treatment in a Preclinical Model of Pancreatic Cancer Using Simultaneous [18F]FDG PET and acidoCEST MRI

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Abstract

Purpose

We sought to determine if the synergy between evaluations of glucose uptake in tumors and extracellular tumor acidosis measured with simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) can improve longitudinal evaluations of the response to metformin treatment.

Procedures

A standard 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET protocol that evaluates glucose uptake in tumors, and a standard acidoCEST MRI protocol that measures extracellular pH (pHe) in tumors, were simultaneously performed to assess eight vehicle-treated (control) mice and eight metformin-treated mice 1 day before treatment, 1 day after initiating daily treatment with metformin, and 7 days after initiating treatment. Longitudinal changes in SUVmax and extracellular pH (pHe) were evaluated for each treatment group, and differences in SUVmax and pHe between metformin-treated and control groups were also evaluated.

Results

MRI acquisition protocols had little effect on the PET count rate, and the PET instrumentation had little effect on image contrast during acidoCEST MRI, verifying that [18F]FDG PET and acidoCEST MRI can be performed simultaneously. The average SUVmax of the tumor model had a significant decrease after 7 days of treatment with metformin, as expected. The average tumor pHe decreased after 7 days of metformin treatment, which reflected the inhibition of the consumption of cytosolic lactic acid caused by metformin. However, the average SUVmax of the tumor model was not significantly different between the metformin-treated and control groups after 7 days of treatment, and average pHe was also not significantly different between these groups. For comparison, the combination of average SUVmax and pHe measurements significantly differed between the treatment group and control group on Day 7.

Conclusions

[18F]FDG PET and acidoCEST MRI studies can be performed simultaneously. The synergistic combination of assessing glucose uptake and tumor acidosis can improve differentiation of a drug-treated group from a control group during drug treatment of a tumor model.

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Acknowledgements

The authors thank Ms. Christine Howison for assistance with PET/MRI studies, and Dr. Neale Hanke for assistance in preparing the tumor model. This research was supported by NIH grants R01 CA167183 and P50 CA95060.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, The University of Arizona, Tucson, AZ, 85721, USA

    Joshua M. Goldenberg

  2. Department of Cancer Systems Imaging, The University of Texas M.D. Anderson Cancer Center, 3SCR4.3642, Unit 1907, Houston, TX, 77054-1901, USA

    Joshua M. Goldenberg & Mark D. Pagel

  3. Banner – University Medical Center, The University of Arizona, Tucson, AZ, 85724, USA

    Julio Cárdenas-Rodríguez

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Correspondence to Mark D. Pagel.

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Goldenberg, J.M., Cárdenas-Rodríguez, J. & Pagel, M.D. Preliminary Results that Assess Metformin Treatment in a Preclinical Model of Pancreatic Cancer Using Simultaneous [18F]FDG PET and acidoCEST MRI. Mol Imaging Biol 20, 575–583 (2018). https://doi.org/10.1007/s11307-018-1164-4

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