Share：
Share this content in WeChat
X
[Chinese][PDF]958232
• Review •
CEST MR contrast agent for pH-sensitive imaging
A Rong  QIAO Wenju  SUN Xiaohong  ZHOU Jiangwei  SUN Xilin 

Cite this article as: A R, Qiao WJ, Sun XH, et al. CEST MR contrast agent for pH-sensitive imaging. Chin J Magn Reson Imaging, 2020, 11(8): 712-716. DOI:10.12015/issn.1674-8034.2020.08.029.


[Abstract] Chemical exchange saturation transfer (CEST) is a magnetic resonance imaging (MRI) methods developed on the basis of magnetization transfer technology and Chemical exchange theory. As an emerging method of MR imaging, CEST MRI has a broad application prospects in molecular imaging and various metabolic studies. Also, extracellular acid pH level of solid tumors is known to be associated with tumor proliferation, metastasis, invasion, radiotherapy and chemotherapy resistance. Therefore, accurate, non-invasive, and dynamic detection of extracellular pH (pHe) value of solid tumors could provide biological information for the detection of tumor acidosis and the efficacy of early anticancer treatment. This review mainly summarizes the application of several pH-sensitive CEST contrast agents alongside their advantages and otherwise.
[Keywords] chemical exchange saturation transfer；tumor acidic microenvironment；contrast agents；pH；magnetic resonance imaging

A Rong TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Harbin 150028, China; Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin 150028, China

QIAO Wenju TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Harbin 150028, China; Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin 150028, China

SUN Xiaohong TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Harbin 150028, China; Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin 150028, China

ZHOU Jiangwei TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Harbin 150028, China; Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin 150028, China

SUN Xilin* TOF-PET/CT/MR Center, The Fourth Hospital of Harbin Medical University, Harbin 150028, China; Molecular Imaging Research Center, Harbin Medical University (MIRC), Harbin 150028, China

*Corresponding to: Sun XL, E-mail: sunxl@ems.hrbmu.edu.cn

Conflicts of interest   None.

ACKNOWLEDGMENTS  This work was part of National Natural Science Foundation of China No. 81627901 National Key Basic Research Development Plan No. 2015CB931800
Received  2020-01-18
Accepted  2020-04-19
DOI: 10.12015/issn.1674-8034.2020.08.029
Cite this article as: A R, Qiao WJ, Sun XH, et al. CEST MR contrast agent for pH-sensitive imaging. Chin J Magn Reson Imaging, 2020, 11(8): 712-716. DOI:10.12015/issn.1674-8034.2020.08.029.

[1]
Ward KM, Aletras AH, Balaban RS. A new class of contrast agents for MRI based on proton chemical exchange dependent saturation transfer (CEST). J Magn Reson, 2000, 143(1): 79-87
[2]
Vinogradov E, Sherry AD, Lenkinski RE. CEST: from basic principles to applications, challenges and opportunities. J Magn Reson, 2013, 229: 155-172.
[3]
Zaiss M, Bachert P. Chemical exchange saturation transfer (CEST) and MR Z-spectroscopy in vivo: a review of theoretical approaches and methods. Phys Med Biol, 2013, 58(22): 221-269.
[4]
Ferrauto G, Di Gregorio E, Ruzza M, et al. Enzyme-responsive LipoCEST agents: assessment of MMP-2 activity by measuring the intra-liposomal water (1) H NMR shift. Angew Chem Int Ed Engl, 2017, 56(40): 12170-12173.
[5]
Chan KW, Liu G, Song X, et al. MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted-cell viability. Nat Mater, 2013, 12(3): 268-275.
[6]
Bar-Shir A, Gilad AA, Chan KW, et al. Metal ion sensing using ion chemical exchange saturation transfer 19F magnetic resonance imaging. J Am Chem Soc, 2013, 135(33): 12164-12167.
[7]
Langereis S, Keupp J, Van Velthoven JL, et al. A temperature-sensitive liposomal 1H CEST and 19F contrast agent for MR image-guided drug delivery. J Am Chem Soc, 2009, 131(4): 1380-1381.
[8]
Sun PZ, Cheung JS, Wang E, et al. Association between pH-weighted endogenous amide proton chemical exchange saturation transfer MRI and tissue lactic acidosis during acute ischemic stroke. J Cereb Blood Flow Metab, 2011, 31(8): 1743-1750.
[9]
Dula AN, Pawate S, Dethrage LM, et al. Chemical exchange saturation transfer of the cervical spinal cord at 7 T. NMR Biomed, 2016, 29(9): 1249-1257.
[10]
Donahue MJ, Donahue PC, Rane S, et al. Assessment of lymphatic impairment and interstitial protein accumulation in patients with breast cancer treatment-related lymphedema using CEST MRI. Magn Reson Med, 2016, 75(1): 345-355.
[11]
Singh A, Haris M, Cai K, et al. Chemical exchange saturation transfer magnetic resonance imaging of human knee cartilage at 3 T and 7 T. Magn Reson Med, 2012, 68(2): 588-594.
[12]
Kogan F, Haris M, Singh A, et al. Method for high-resolution imaging of creatine in vivo using chemical exchange saturation transfer. Magn Reson Med, 2014, 71(1): 164-172.
[13]
Yan K, Fu Z, Yang C, et al. Assessing amide proton transfer (APT) MRI contrast origins in 9 L gliosarcoma in the rat brain using proteomic analysis. Mol Imaging Biol, 2015, 17(4): 479-487.
[14]
Bose S, Le A. Glucose metabolism in cancer. Adv Exp Med Biol, 2018, 1063: 3-12.
[15]
Swietach P, Vaughan-Jones RD, Harris AL, et al. The chemistry, physiology and pathology of pH in cancer. Philos Trans R Soc Lond B Biol Sci, 2014, 369(1638): 20130099.
[16]
Nomura K, Hayakawa K, Tatsumi H, et al. Actin-interacting protein 1 promotes disassembly of actin-depolymerizing factor/cofilin-bound actin filaments in a pH-dependent manner. J Biol Chem, 2016, 291(10): 5146-5156.
[17]
Johnson LL, Pavlovsky AG, Johnson AR, et al. A rationalization of the acidic pH dependence for stromelysin-1 (Matrix metalloproteinase-3) catalysis and inhibition. J Biol Chem, 2000, 275(15): 11026-11033.
[18]
Kato Y, Ozawa S, Miyamoto C, et al. Acidic extracellular microenvironment and cancer. Cancer Cell Int, 2013, 13(1): 89.
[19]
Anemone A, Consolino L, Arena F, et al. Imaging tumor acidosis: a survey of the available techniques for mapping in vivo tumor pH. Cancer Metastasis Rev, 2019, 38(1-2): 25-49.
[20]
Goldenberg JM, Pagel MD. Assessments of tumor metabolism with CEST MRI. NMR Biomed, 2019, 32(10): e3943.
[21]
Longo DL, Sun PZ, Consolino L, et al. A general MRI-CEST ratiometric approach for pH imaging: demonstration of in vivo pH mapping with iobitridol. J Am Chem Soc, 2014, 136(41): 14333-14336.
[22]
Mcvicar N, Li AX, Goncalves DF, et al. Quantitative tissue pH measurement during cerebral ischemia using amine and amide concentration-independent detection (AACID) with MRI. J Cereb Blood Flow Metab, 2014, 34(4): 690-698.
[23]
Gillies RJ, Raghunand N, Garcia-Martin ML, et al. pH imaging. A review of pH measurement methods and applications in cancers. IEEE Eng Med Biol Mag, 2004, 23(5): 57-64.
[24]
Zhou J, Payen JF, Wilson DA, et al. Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI. Nat Med, 2003, 9(8): 1085-1090.
[25]
Harris RJ, Cloughesy TF, Liau LM, et al. Simulation, phantom validation, and clinical evaluation of fast pH-weighted molecular imaging using amine chemical exchange saturation transfer echo planar imaging (CEST-EPI) in glioma at 3 T. NMR Biomed, 2016, 29(11): 1563-1576.
[26]
Lindeman LR, Randtke EA, High RA, et al. A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo pH. Magn Reson Med, 2018, 79(5): 2766-2772.
[27]
Pereira PC, Miranda DM, Oliveira EA, et al. Molecular pathophysiology of renal tubular acidosis. Curr Genomics, 2009, 10(1): 51-59.
[28]
Sun PZ, Longo DL, Hu W, et al. Quantification of iopamidol multi-site chemical exchange properties for ratiometric chemical exchange saturation transfer (CEST) imaging of pH. Phys Med Biol, 2014, 59(16): 4493-4504.
[29]
Jones KM, Randtke EA, Howison CM, et al. Measuring extracellular pH in a lung fibrosis model with acidoCEST MRI. Mol Imaging Biol, 2015, 17(2): 177-184.
[30]
Longo DL, Dastru W, Digilio G, et al. Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T. Magn Reson Med, 2011, 65(1): 202-211.
[31]
Chen LQ, Howison CM, Jeffery JJ, et al. Evaluations of extracellular pH within in vivo tumors using acido CEST MRI. Magn Reson Med, 2014, 72(5): 1408-1417.
[32]
Delli Castelli D, Ferrauto G, Cutrin JC, et al. In vivo maps of extracellular pH in murine melanoma by CEST-MRI. Magn Reson Med, 2014, 71(1): 326-332.
[33]
Sheth VR, Li Y, Chen LQ, et al. Measuring in vivo tumor pHe with CEST-FISP MRI. Magn Reson Med, 2012, 67(3): 760-768.
[34]
Delli Castelli D, Terreno E, Aime S. Yb(Ⅲ)-HPDO3A: a dual pH-and temperature-responsive CEST agent. Angew Chem Int Ed Engl, 2011, 50(8): 1798-1800.
[35]
Wu Y, Soesbe TC, Kiefer GE, et al. A responsive europium(Ⅲ) chelate that provides a direct readout of pH by MRI. J Am Chem Soc, 2010, 132(40): 14002-14003.
[36]
Chen LQ, Howison CM, Spier C, et al. Assessment of carbonic anhydrase IX expression and extracellular pH in B-cell lymphoma cell line models. Leuk Lymphoma, 2015, 56(5): 1432-1439.
[37]
Longo DL, Michelotti F, Consolino L, et al. In vitro and in vivo assessment of nonionic iodinated radiographic molecules as chemical exchange saturation transfer magnetic resonance imaging tumor perfusion agents. Invest Radiol, 2016, 51(3): 155-162.
[38]
Chen Z, Li Y, Airan R, et al. CT and CEST MRI bimodal imaging of the intratumoral distribution of iodinated liposomes. Quant Imaging Med Surg, 2019, 9(9): 1579-1591.
[39]
Bellin MF, Stacul F, Webb JA, et al. Late adverse reactions to intravascular iodine based contrast media: an update. Eur Radiol, 2011, 21(11): 2305-2310.
[40]
Yang X, Song X, Ray Banerjee S, et al. Developing imidazoles as CEST MRI pH sensors. Contrast Media Mol Imaging, 2016, 11(4): 304-312.
[41]
Yang X, Song X, Li Y, et al. Salicylic acid and analogues as diaCEST MRI contrast agents with highly shifted exchangeable proton frequencies. Angew Chem Int Ed Engl, 2013, 52(31): 8116-8119.
[42]
Song X, Yang X, Ray Banerjee S, et al. Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen. Contrast Media Mol Imaging, 2015, 10(1): 74-80.
[43]
Ni D, Shen Z, Zhang J, et al. Integrating anatomic and functional dual-mode magnetic resonance imaging: Design and applicability of a bifunctional contrast agent. ACS Nano, 2016, 10(3): 3783-3790.
[44]
Sherry AD, Wu Y. The importance of water exchange rates in the design of responsive agents for MRI. Curr Opin Chem Biol, 2013, 17(2): 167-174.
[45]
Aime S, Barge A, Delli Castelli D, et al. Paramagnetic lanthanide(Ⅲ ) complexes as pH-sensitive chemical exchange saturation transfer (CEST) contrast agents for MRI applications. Magn Reson Med, 2002, 47(4): 639-648.
[46]
Aime S, Delli Castelli D, Terreno E. Novel pH-reporter MRI contrast agents. Angew Chem Int Ed Engl, 2002, 41(22): 4334-4336.
[47]
Rancan G, Delli Castelli D, Aime S. MRI CEST at 1T with large microeff Ln(3+) complexes T m(3+)-HPDO3A: An efficient MRI pH reporter. Magn Reson Med, 2016, 75(1): 329-336.
[48]
Liu G, Li Y, Sheth VR, et al. Imaging in vivo extracellular pH with a single paramagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. Mol Imaging, 2012, 11(1): 47-57.
[49]
Wu Y, Zhang S, Soesbe TC, et al. pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent. Magn Reson Med, 2016, 75(6): 2432-2441.
[50]
Huang Y, Coman D, Ali MM, et al. Lanthanide ion (Ⅲ) complexes of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraaminophosphonate for dual biosensing of pH with chemical exchange saturation transfer (CEST) and biosensor imaging of redundant deviation in shifts (BIRDS). Contrast Media Mol Imaging, 2015, 10(1): 51-58.
[51]
Coman D, Huang Y, Rao JU, et al. Imaging the intratumoral-peritumoral extracellular pH gradient of gliomas. NMR Biomed, 2016, 29(3): 309-319.
[52]
Gianolio E, Porto S, Napolitano R, et al. Relaxometric investigations and MRI evaluation of a liposome-loaded pH-responsive gadolinium(Ⅲ) complex. Inorg Chem, 2012, 51(13): 7210-7217.

PREV The advances in cardiovascular magnetic resonance imaging for light-chain and transthyretin-related amyloidosis
NEXT Research status of Gadolinium-based contrast on safety
  


LINK


Tel & Fax: +8610-67113815    E-mail: editor@cjmri.cn