Review Article
Evaluating pH in the Extracellular Tumor Microenvironment Using CEST MRI and Other Imaging Methods
Table 2
Summary of CEST methods to detect pH.
| | Agent | Range | Admin. | Spatial res., cm3 | Temporal res. | CEST acquisition | Mouse model | Reference |
| Yb-DOTAM-Gly &
Eu-DOTAM-Gly | 6.5–8.0 | — | — | — | — | In vitro | [54] | | Pr-DOTAM-Gly | 5.5–7.5 | — | — | — | — | In vitro | [55, 56] | | Nd-DOTAM-Gly | 6–7.5 | — | — | — | — | In vitro | [55] | | Eu-DOTAM-Gly | 6–7.5 | — | — | — | — | In vitro | [55] | | Dendrimer Yb-DOTAM | 5–7 | — | — | — | — | In vitro | [57] | | 5,6-Dihydrouracil | 6.5–7.0 | — | — | — | — | In vitro | [58] |
| | APT | pH > 5.0 | Endogenous | 1.56 × 10−3 | 4 + 10 s
(2 offset) | CEST-EPI
0.6 µT | Ischemic rat brain,
6.52 ± 0.32 | [59] | APT with
creatine | 5.2–6.4 | Endogenous | 2.5 × 10−3 | 7.5 + 15 s
(2 offset) | CEST-EPI
0.6 µT | Healthy human brain | [60] | | Yb-HPDO3A | 5.2–6.7 | i.v. 1.2 mmol/kg | 2.2 × 10−3 | 5 min | CEST-RARE, 24 µT | Melanoma
Early 2 mm dia 6.1
Late 10 mm dia 5.8 | [61] | | Tm-DOTAM-Gly-Lys | 6.0–8.0 | Direct inj 50 μL 100 mM | 1.28 × 10−3 | 26 min 36 s | CEST-RARE
14 µT | Leg muscle
7.2 ± 0.2 | [62, 63] | | Yb-DO3A-oAA | 6.1–7.75
6.35–7.57
6.34–7.82 ± 0.21 | 50 μL of 60 mM direct injection into flank tumor
i.v. 50 μL 100 mM | 1.17 × 10−3 | 5.2 min | CEST-FISP
20 µT | MCF-7,
pHe < 6.5
37°C
MDA-MB-231 ROI:
6.82 ± 0.21
Pixel: 6.8 ± 0.4 | [64, 65] | | Iopamidol | 5.5–7.7 | 2.0 mM/kg | 4.39 × 10−4 | 4 min 18 s | CEST-RARE
3 µT | Acute kidney injury of mouse, healthy kidney 6.71 ± 0.16, after injury, pH 7.09 ± 0.10 | [66, 67] | | Iopromide | 6.2–7.2 | 12 mM/kg | 1.25 × 10−4 | 4 min 50 s | CEST-FISP
2.8 µT | MDA-MB-231
pH 6.5–7.2 | [68] |
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