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Open AccessOpen Access JUSTC Chemistry; Life Sciences 03 July 2023

Recent progress on diaCEST MRI for tumor imaging

  • Department of Chemistry, University of Science and Technology of China, Hefei 230026, China

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https://doi.org/10.52396/JUSTC-2023-0027
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  • Author Bio:

    Qin Yu is currently a postgraduate student at the School of Chemistry and Materials Science, University of Science and Technology of China, under the supervision of Prof. Yue Yuan. His research interests include diamagnetism chemical exchange saturated transfer magnetic resonance imaging contrast agents and supramolecular hydrogel

    Yue Yuan received her Ph.D. degree in Analytical Chemistry from the University of Science and Technology of China. She is currently a Professor at the University of Science and Technology of China. Her research mainly focuses on diaCEST MRI agents and intracellular self-assembly probes for tumor diagnosis and treatment

  • Corresponding author: E-mail: yueyuan@ustc.edu.cn
  • Received Date: 22 February 2023
  • Accepted Date: 26 April 2023
    • Available Online: 03 July 2023
    Abstract

  • Abstract

    Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an advanced imaging method that probes the chemical exchange between bulk water protons and exchangeable solute protons. This chemical exchange decreases the MR signal of water and reveals the distribution and concentration of certain endogenous biomolecules or extrogenous contrast agents in organisms with high sensitivity and spatial resolution. The CEST signal depends not only on the concentration of the CEST contrast agent and external magnetic field but also on the surrounding environments of the contrast agent, such as pH and temperature, thus enabling CEST MRI to monitor pH, temperature, metabolic level, and enzyme activity in vivo. In this review, we discuss the principle of CEST MRI and mainly summarize the recent progress of diamagnetic CEST (diaCEST) contrast agents on tumor imaging, diagnosis, and therapy effect evaluation.

    Graphical abstract

    Three different diaCEST contrast agents and their chemical exchange saturation transfer process with bulk water protons.

    Abstract

    Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is an advanced imaging method that probes the chemical exchange between bulk water protons and exchangeable solute protons. This chemical exchange decreases the MR signal of water and reveals the distribution and concentration of certain endogenous biomolecules or extrogenous contrast agents in organisms with high sensitivity and spatial resolution. The CEST signal depends not only on the concentration of the CEST contrast agent and external magnetic field but also on the surrounding environments of the contrast agent, such as pH and temperature, thus enabling CEST MRI to monitor pH, temperature, metabolic level, and enzyme activity in vivo. In this review, we discuss the principle of CEST MRI and mainly summarize the recent progress of diamagnetic CEST (diaCEST) contrast agents on tumor imaging, diagnosis, and therapy effect evaluation.

    • Public Summary

    • We summarize several types of diaCEST MRI agents, including glucose, amide protons, salicylic acid and their analogs, which are promising for the diagnosis of tumors in CEST MRI.
    • We present an in-depth discussion of the applications of these contrast agents in tumor imaging in recent years, such as colorectal tumors and brain tumors.
    • We evaluate these three different types of contrast agents and point out their advantages and disadvantages in CEST MRI.

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    • References(79)
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    Figure  1.  The underlying principle of CEST MRI via a two-pool model.

    Figure  2.  The signal analysis and related spectrum. (a) The exchange of exchangeable solute protons and bulk water protons leads to a decrease in bulk water signals. Black line: signal intensity of water before RF irradiation; red line: signal intensity of water after RF irradiation. (b) Z-spectrum or CEST spectrum. (c) MTR asymmetry analysis.

    Figure  3.  Three different diaCEST contrast agents and their MTRasym signals: Salicylic acid (1), barbituric acid (2), and D-glucose (3). Reprinted with permission from Ref. [8]. Copyright 2013, Springer Nature Limited.

    Figure  4.  Analysis of mouse tumors by paraCEST agents. (a) CEST serial MRI of tumor-bearing mice after injection of two different paraCEST agents and (b) quantitative CEST MRI signals of tumors at different time points. Reprinted with permission from Ref. [13]. Copyright 2009, American Chemical Society.

    Figure  5.  Main structures of salicylic acid-based diaCEST contrast agents. Reproduced with permission from Ref. [25]. Copyright 2016, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

    Figure  6.  Representative CEST MRI images. (a) The anatomical image of mouse, (b) glucoCEST images before infusing agents, and (c) glucoCEST images after infusing; (d) GlucoCEST images, [18F]FDG images, and fluorescence images of the same tumor section; (e) the anatomical image and (f) CEST MRI of tumor after injecting 3-OMG for 3–8 min. (a–c) Reprinted with permission from Ref. [17]. Copyright 2012, Wiley Periodicals, Inc. (d) Reprinted with permission from Ref. [28]. Copyright 2013, Springer Nature America, Inc. (e, f) Reprinted with permission from Ref. [32]. Copyright 2019, International Society for Magnetic Resonance in Medicine.

    Figure  7.  Several images of mouse brains. (a) The glucoCEST imaging, (b) t-map images, and (c) MTRasym analysis of rat brain before and after the injection of xylose. (d) T2-weighted and mannose-weighted CEST MR images of mice after intrastriatal hMSC transplantation. (a–c) Reprinted with permission from Ref. [40]. Copyright 2021, International Society for Magnetic Resonance in Medicine. (d) Reprinted with permission from Ref. [45]. Copyright 2022, The Author(s), under exclusive license to Springer Nature Limited.

    Figure  8.  Representative T1/T2 and CEST MRI images of tumors at different sites. (a) T2-weighted, T1-weighted and APT-weighted images of rat brain tumors; (b) T2-weighted anatomical image and amide proton transfer-weighted image of pleomorphic adenoma in the right parotid gland. (a) Reprinted with permission from Ref. [14]. Copyright 2003, Wiley-Liss, Inc. (b) Reprinted with permission from Ref. [46]. Copyright 2014, John Wiley & Sons, Ltd.

    Figure  9.  Different MRI images and related analysis. (a) The contrast-enhanced T1-weighted image, (b) dynamic susceptibility contrast (DSC)-enhanced MR image, and (c) APT image of TP. (d) The APTw Z-spectrum and (e) MTRasym result of a stroke patient brain. The APTw image of the brain of (f) a normal person and (g) an AD patient. (a–c) Reprinted with permission from Ref. [49]. Copyright 2016, European Society of Radiology. (d–e) Reprinted with permission from Ref. [55]. Copyright 2007, Wiley-Liss, Inc. (f, g) Reprinted with permission from Ref. [51]. Copyright 2015, Chinese Medical Association.

    Figure  10.  MRI images and related analysis of mice administered SA. (a) T2w image, (b) overlay CEST image preinjection, and (c) overlay CEST image at 7 min postinjection of mice administered SA; (d) Z-spectra and MTRasym for the right kidney before injection (black) and 7 min postinjection (light blue); (e) MTRasym values of the left kidney and right kidney at different time points after SA injection. Reprinted with permission from Ref. [8]. Copyright 2013, Springer Nature Limited.

    Figure  11.  Several applications of SA, Olsa and other probes. (a) The T2w image and MTRasym image of SA-conjugated dendrimers in vivo: preinjection, 30 min postinjection, and 60 min postinjection; (b) the SA-based polymeric diaCEST agent and its CEST MRI in PSMA(+) PC3 PIP and PSMA(−) PC3 flu tumors; (c) the chemical structure and (d) self-assembly mechanism of Olsa-RVRR in tumor cells. (e) The principle of the cathepsin B-responsive CEST probe; (f) CEST spectra of the cathepsin B-responsive CEST probe before and after cleavage with cathepsin B. (a) Reprinted with permission from Ref. [65]. Copyright 2016, American Chemical Society. (b) Reprinted with permission from Ref. [66]. Copyright 2018, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. (c, d) Reprinted with permission from Ref. [22]. Copyright 2019, The Author(s), under exclusive license to Springer Nature Limited. (e, f) Reprinted with permission from Ref. [73]. Copyright 2021, American Chemical Society.

    [1]
    van Zijl P C M, Yadav N N. Chemical exchange saturation transfer (CEST): What is in a name and what isn’t? Magnetic Resonance in Medicine, 2011, 65 (4): 927–948. doi: 10.1002/mrm.22761
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