Investigative Magnetic Resonance Imaging

Korean Society of Magnetic Resonance in Medicine (대한자기공명의과학회)
권호 표지
DOI QR코드

DOI QR Code

Diagnostic Significance of pH-Responsive Gd3+-Based T1 MR Contrast Agents

  • Received : 2018.08.10
  • Accepted : 2019.02.01
  • Published : 2019.03.29
Download PDF
⟨ Previous Next ⟩

Abstract

We discuss recent advances in Gd-based $T_1$-weighted MR contrast agents for the mapping of cellular pH. The pH plays a critical role in various biological processes. During the past two decades, several MR contrast agents of strategic importance for pH-mapping have been developed. Some of these agents shed light on the pH fluctuation in the tumor microenvironment. A pH-responsive self-assembled contrast agent facilitates the visualization of tumor size as small as $3mm^3$. Optimization of various parameters is crucial for the development of pH-responsive contrast agents. In due course, the new contrast agents may provide significant insight into pH fluctuations in the human body.

Keywords

References

  1. Boron WF, Boulpaep EL. Medical physiology: a cellular and molecular approach. Philadelphia: Saunders/Elsevier, 2008
  2. Lambers H, Piessens S, Bloem A, Pronk H, Finkel P. Natural skin surface pH is on average below 5, which is beneficial for its resident flora. Int J Cosmet Sci 2006;28:359-370 https://doi.org/10.1111/j.1467-2494.2006.00344.x
  3. Han J, Burgess K. Fluorescent indicators for intracellular pH. Chem Rev 2010;110:2709-2728 https://doi.org/10.1021/cr900249z
  4. Adrogue HJ, Wesson DE. Overview of acid base disorders. In: Adrogue HJ, Wesson DE, eds. Blackwell's basics of medicine. Acid-base. Boston: Blackwell Science, 1994;49-133
  5. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324:1029-1033 https://doi.org/10.1126/science.1160809
  6. Behne MJ, Barry NP, Hanson KM, et al. Neonatal development of the stratum corneum pH gradient: localization and mechanisms leading to emergence of optimal barrier function. J Invest Dermatol 2003;120:998-1006 https://doi.org/10.1038/jid.2003.11
  7. Ilic D, Mao-Qiang M, Crumrine D, et al. Focal adhesion kinase controls pH-dependent epidermal barrier homeostasis by regulating actin-directed Na+/H+ exchanger 1 plasma membrane localization. Am J Pathol 2007;170:2055-2067 https://doi.org/10.2353/ajpath.2007.061277
  8. Okabe Y, Medzhitov R. Tissue-specific signals control reversible program of localization and functional polarization of macrophages. Cell 2014;157:832-844 https://doi.org/10.1016/j.cell.2014.04.016
  9. Lee MH, Park N, Yi C, et al. Mitochondria-immobilized pH-sensitive off-on fluorescent probe. J Am Chem Soc 2014;136:14136-14142 https://doi.org/10.1021/ja506301n
  10. Chen G, Fu Q, Yu F, et al. Wide-acidity-range pH fluorescence probes for evaluation of acidification in mitochondria and digestive tract mucosa. Anal Chem 2017;89:8509-8516 https://doi.org/10.1021/acs.analchem.7b02164
  11. Podder A, Won M, Kim S, et al. A two-photon fluorescent probe records the intracellular pH through 'OR' logic operation via internal calibration. Sensors and Actuators B: Chemical 2018;268:195-204 https://doi.org/10.1016/j.snb.2018.04.092
  12. Raghunand N, Altbach MI, van Sluis R, et al. Plasmalemmal pH-gradients in drug-sensitive and drug-resistant MCF-7 human breast carcinoma xenografts measured by 31P magnetic resonance spectroscopy. Biochem Pharmacol 1999;57:309-312 https://doi.org/10.1016/S0006-2952(98)00306-2
  13. Mason RP. Transmembrane pH gradients in vivo: measurements using fluorinated vitamin B6 derivatives. Curr Med Chem 1999;6:481-499
  14. Ojugo AS, McSheehy PM, McIntyre DJ, et al. Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous (19)F and (31)P probes. NMR Biomed 1999;12:495-504 https://doi.org/10.1002/(SICI)1099-1492(199912)12:8<495::AID-NBM594>3.0.CO;2-K
  15. van Sluis R, Bhujwalla ZM, Raghunand N, et al. In vivo imaging of extracellular pH using 1H MRSI. Magn Reson Med 1999;41:743-750 https://doi.org/10.1002/(SICI)1522-2594(199904)41:4<743::AID-MRM13>3.0.CO;2-Z
  16. Garcia-Martin ML, Herigault G, Remy C, et al. Mapping extracellular pH in rat brain gliomas in vivo by 1H magnetic resonance spectroscopic imaging: comparison with maps of metabolites. Cancer Res 2001;61:6524-6531
  17. Vermathen P, Capizzano AA, Maudsley AA. Administration and (1)H MRS detection of histidine in human brain: application to in vivo pH measurement. Magn Reson Med 2000;43:665-675 https://doi.org/10.1002/(SICI)1522-2594(200005)43:5<665::AID-MRM8>3.0.CO;2-3
  18. Mori S, Eleff SM, Pilatus U, Mori N, van Zijl PC. Proton NMR spectroscopy of solvent-saturable resonances: a new approach to study pH effects in situ. Magn Reson Med 1998;40:36-42 https://doi.org/10.1002/mrm.1910400105
  19. Ward KM, Balaban RS. Determination of pH using water protons and chemical exchange dependent saturation transfer (CEST). Magn Reson Med 2000;44:799-802 https://doi.org/10.1002/1522-2594(200011)44:5<799::AID-MRM18>3.0.CO;2-S
  20. Goldman MR, Brady TJ, Pykett IL, et al. Quantification of experimental myocardial infarction using nuclear magnetic resonance imaging and paramagnetic ion contrast enhancement in excised canine hearts. Circulation 1982;66:1012-1016 https://doi.org/10.1161/01.CIR.66.5.1012
  21. Caravan P. Strategies for increasing the sensitivity of gadolinium based MRI contrast agents. Chem Soc Rev 2006;35:512-523 https://doi.org/10.1039/b510982p
  22. Koenig SH. A novel derivation of the Solomon-Bloembergen-Morgan equations: application to solvent relaxation by Mn2+-protein complexes. J Magn Reson 1978;31:1-10 https://doi.org/10.1016/0022-2364(78)90163-4
  23. Westlund PO. A generalized Solomon-Bloembergen-Morgan theory for arbitrary electron spin quantum number S - the dipole-dipole coupling between a nuclear spin I = 1/2 and an electron spin system S = 5/2. Mol Phys 1995;85:1165-1178 https://doi.org/10.1080/00268979500101741
  24. Kowalewski J, Luchinat C, Nilsson T, Parigi G. Nuclear spin relaxation in paramagnetic systems: electron spin relaxation effects under near-red field limit conditions and beyond. J Phys Chem A 2002;106:7376-7382 https://doi.org/10.1021/jp020608p
  25. Yin J, Chen D, Zhang Y, Li C, Liu L, Shao Y. MRI relaxivity enhancement of gadolinium oxide nanoshells with a controllable shell thickness. Phys Chem Chem Phys 2018;20:10038-10047 https://doi.org/10.1039/C8CP00611C
  26. Zech SG, Eldredge HB, Lowe MP, Caravan P. Protein binding to lanthanide(III) complexes can reduce the water exchange rate at the lanthanide. Inorg Chem 2007;46:3576-3584 https://doi.org/10.1021/ic070011u
  27. Werner EJ, Datta A, Jocher CJ, Raymond KN. High-relaxivity MRI contrast agents: where coordination chemistry meets medical imaging. Angew Chem Int Ed Engl 2008;47:8568-8580 https://doi.org/10.1002/anie.200800212
  28. Zhang S, Wu K, Sherry AD. A novel pH-Sensitive MRI contrast agent. Angew Chem Int Ed Engl 1999;38:3192-3194 https://doi.org/10.1002/(SICI)1521-3773(19991102)38:21<3192::AID-ANIE3192>3.0.CO;2-#
  29. Ali MM, Woods M, Caravan P, et al. Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent. Chemistry 2008;14:7250-7258 https://doi.org/10.1002/chem.200800402
  30. Garcia-Martin ML, Martinez GV, Raghunand N, Sherry AD, Zhang S, Gillies RJ. High resolution pH(e) imaging of rat glioma using pH-dependent relaxivity. Magn Reson Med 2006;55:309-315 https://doi.org/10.1002/mrm.20773
  31. Aime S, Fedeli F, Sanino A, Terreno E. A R2/R1 ratiometric procedure for a concentration-independent, pH-responsive, Gd(III)-based MRI agent. J Am Chem Soc 2006;128:11326-11327 https://doi.org/10.1021/ja062387x
  32. Toth E, Bolskar RD, Borel A, et al. Water-soluble gadofullerenes: toward high-relaxivity, pH-responsive MRI contrast agents. J Am Chem Soc 2005;127:799-805 https://doi.org/10.1021/ja044688h
  33. Bhuniya S, Moon H, Lee H, et al. Uridine-based paramagnetic supramolecular nanoaggregate with high relaxivity capable of detecting primitive liver tumor lesions. Biomaterials 2011;32:6533-6540 https://doi.org/10.1016/j.biomaterials.2011.05.054
  34. Woods M, Kiefer GE, Bott S, et al. Synthesis, relaxometric and photophysical properties of a new pH-responsive MRI contrast agent: the effect of other ligating groups on dissociation of a p-nitrophenolic pendant arm. J Am Chem Soc 2004;126:9248-9256 https://doi.org/10.1021/ja048299z
  35. Frullano L, Catana C, Benner T, Sherry AD, Caravan P. Bimodal MR-PET agent for quantitative pH imaging. Angew Chem Int Ed Engl 2010;49:2382-2384 https://doi.org/10.1002/anie.201000075
  36. Moriggi L, Yaseen MA, Helm L, Caravan P. Serum albumin targeted, pH-dependent magnetic resonance relaxation agents. Chemistry 2012;18:3675-3686 https://doi.org/10.1002/chem.201103344
  37. Kim KS, Park W, Hu J, Bae YH, Na K. A cancer-recognizable MRI contrast agents using pH-responsive polymeric micelle. Biomaterials 2014;35:337-343 https://doi.org/10.1016/j.biomaterials.2013.10.004