MRI Reporter Genes for Noninvasive Molecular Imaging
Abstract
:1. Introduction
2. Commonly Used MRI Reporter Genes
2.1. Ferritin
2.2. TfR
2.3. TYR
2.4. β-Galactosidase
2.5. Lysine Rich-Protein (LRP)
3. Multimodality Imaging Reporter Genes
3.1. Single Reporter Genes for Multimodality Imaging
3.1.1. The Organic Anion Transporting Polypeptides (Oatp) 1
3.1.2. LacZ
3.1.3. TYR
3.1.4. Combination of Single Reporter Gene and Contrast Agents for Multimodality Imaging
3.2. Fusion Reporter Gene Used for Multimodality Imaging
4. Conclusions and Perspectives
Acknowledgments
Conflicts of Interest
References
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Gene/Protein | Contrast Mechanism | Observed Change | Test System | Ref. |
---|---|---|---|---|
Ferritin | Sequesters iron from labile intracellular iron pool and acts as an intracellular SPIO analog | T2 changes from 45 to 20 ms with 30 µg Ferritin expressed per mg of total protein (14 T) | Cell culture; viral-mediated transfection in mouse brain | [16] |
Transferrin receptor (TfR) | Transferrin-conjugated SPIO particles are internalized by ectopically expressed TfR on transfected cells | 50% change in T2-weighted MRI signal (3 mg iron injected per mouse, 7.1 T) | Mice implanted with TfR-expressing gliosarcoma cells | [17] |
Tyrosinase (TYR) | TYR produces melanin to chelate metal ions (Fe3+) | 37% increase in T1-weighted MRI signal (1.5 T) | Transfected mouse fibroblasts and HEK cells | [18] |
β-galactosidase | Expressed β-gal cleaves a caged synthetic Gd3+ compounds | 60% T1-weighted signal increase (3.2 nmol per frog embryo, 12 T) | Xenopuslaevisembryos transfected withLacZ | [19] |
Lysine rich-protein (LRP) | Chemical exchange saturation transfer (CEST) | 134% signal increase (6 days after 5 × 104 cells transplanted into the striatum of NOD-SCID male mice, 11.7 T) | Mice implanted with LRP and EGFP expressing xenografts respectively in opposite hemispheres | [20] |
Molecular Imaging Methods | Resolution | Depth | Sensitivity | Cost | Potential Clinical Uses |
---|---|---|---|---|---|
OI | 1–5 mm | up to < 5 cm | 10−9–10−12 mol/L | low cost | very low |
MRI | 10–100 µm | no limit | 10−3–10−5 mol/L | high cost | yes |
PET | 1–2 mm | no limit | 10−10–10−12 mol/L | high cost | yes |
SPECT | 0.3–1 mm | no limit | 10−10–10−12 mol/L | high cost | yes |
Single/Fusion Reporter Gene | Gene/Protein | Contrast Mechanism | Imaging Method | Ref. |
---|---|---|---|---|
Single reporter gene | Oatp1 | (1) Transfer MRI contrast agents (2) Mediate uptake of Gd3+ or 111In based hepatotrophic contrast agents | MRI (T1WI) SPECT | [79,80] |
LacZ | (1) Express β-gal to cleave Gd3+ compounds (2) Visualize lacZ gene expression with activated fluorescent contrast agents | MRI (T1WI) NIR | [4,5,56] | |
TYR | (1) Broad optical absorption for photoacoustic effect (2) Chelate metal ions (Fe3+) providing contrast for MRI (3) Melanin-avid PET probes, 18F-P3BZA | PAI MRI (T2WI) PET | [52,81,82,83] | |
Multimodality reporter gene | Single reporter gene and contrast agent | Sodium iodide symporter (NIS) gene and iron oxide | PET MRI | [84] |
Fusion reporter gene | Ferritin gene fused with green fluorescent protein gene | MRI NIR | [74] |
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Yang, C.; Tian, R.; Liu, T.; Liu, G. MRI Reporter Genes for Noninvasive Molecular Imaging. Molecules 2016, 21, 580. https://doi.org/10.3390/molecules21050580
Yang C, Tian R, Liu T, Liu G. MRI Reporter Genes for Noninvasive Molecular Imaging. Molecules. 2016; 21(5):580. https://doi.org/10.3390/molecules21050580
Chicago/Turabian StyleYang, Caixia, Rui Tian, Ting Liu, and Gang Liu. 2016. "MRI Reporter Genes for Noninvasive Molecular Imaging" Molecules 21, no. 5: 580. https://doi.org/10.3390/molecules21050580
APA StyleYang, C., Tian, R., Liu, T., & Liu, G. (2016). MRI Reporter Genes for Noninvasive Molecular Imaging. Molecules, 21(5), 580. https://doi.org/10.3390/molecules21050580