Review Article
Evaluating pH in the Extracellular Tumor Microenvironment Using CEST MRI and Other Imaging Methods
Table 1
Summary of pH measurement methods with various instruments.
| Method | Sampling time Spatial resolution Agent [] | Advantages and disadvantages | Reference |
| Microelectrode | Fast, sec Localized measurement No agent required | Fast; accurate if calibrated with an external buffer Limited to surface-accessible tumors; requires MRI to guide electrodes into tumors | [16–18] |
| Fluorescence imaging | Fast, sec 5 µm µM–nM | Sensitive; low cost; can be used during clinical fluorescence guided surgery Limited to surface-accessible tumors | [14, 19–21, 25–29] |
| PET | 10 min 2 mm nM | Fast; whole body imaging Requires radioactive isotope; coarse resolution; and limited accuracy | [22–24, 31] |
| 1H MRS | >30 min 1 mm3 mM | Simultaneous measurement of pHe and detection of metabolites Poor sensitivity; some agents are pH buffers that change tissue pHe | [34, 39, 40] |
| 31P MRS | 40 min 1 cm3 mM | Can simultaneously measure pHi and pHe Requires a MRI transceiver coil | [41, 43–46] |
| 19F MRS | 5 min 1 cm3 µM–mM | Fast; good sensitivity Requires a MRI transceiver coil | [42, 47, 49] |
| Hyperpolarized 13C MRS | 5 sec 0.375 mm3 mM | Very fast Requires a MRI transceiver coil; requires a hyperpolarizer instrument Short hyperpolarized life time; Measures pHi and pHe | [48] |
| pH dependent relaxation | <1 min 0.1 mm3 mM | Fast; high resolution Requires a cocktail of contrast agents | [50–53] |
| CEST MRI | ~5 min µm–mm mM | Good specificity Poor sensitivity | [37] |
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