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Published on: April 19, 2021
Ligand-based molecular MRI: O-17 JJVCPE amyloid imaging in transgenic mice
Kiyotaka Suzuki1, Hironaka Igarashi1, Vincent J Huber1
1Center for Integrated Human Brain Science Brain Research Institute, University of Niigata.
Background:
Development of molecular MR imaging (MRI) similar to PET imaging using contrast agents such as gadolinium as probe have been inherently hampered by incompatibility between potential probe (charged molecules) and membrane permeability. Nevertheless, considering the inherent spatial resolution limit for PET of 700μ, the superior microscopic resolution of MRI of 4 μ presents a strong incentive for research into ligand-based molecular MRI.
Methods:
(17) O exhibits JJ vicinal coupling with a covalently bound proton in a hydroxyl group. This (17) O coupled proton can be ionized in water solution and interexchange with other water protons. This property can be utilized as "probe" in T2-weighted imaging and developed into ligand-based molecular MRI. We examined β-amyloid distribution in human APP overexpressed transgenic mice in vivo following injection of (17) O labeled Pittsburg compound B ((17) O-PiB).
Results:
JJVCPE imaging successfully imaged (17) O-PiB, unequivocally establishing that (17) O JJVCPE imaging can be developed into PET-like molecular MRI in clinical medicine.
Conclusions:
The study represents the first successful ligand-based molecular MRI in vivo. This is also the first in vivo amyloid imaging using MRI. High-resolution molecular MRI with high specificity under clinical settings, such as in vivo microscopic imaging of senile plaque, is a foreseeable aim.
Insights
This study introduces a novel ligand-based molecular MRI technique for in vivo imaging. The method successfully visualized beta-amyloid, paving the way for high-resolution MRI in clinical settings.
Area of Science:
- Biomedical Imaging
- Molecular Imaging
- Neuroimaging
Background:
- Molecular Magnetic Resonance Imaging (MRI) development is hindered by contrast agent incompatibility with cell membranes.
- Positron Emission Tomography (PET) has limited spatial resolution (700μ), motivating research into MRI's superior microscopic resolution (4μ).
Purpose of the Study:
- To develop a ligand-based molecular MRI technique for in vivo imaging.
- To overcome limitations of current molecular imaging modalities.
- To enable high-resolution imaging of molecular targets like beta-amyloid.
Main Methods:
- Utilized (17)O-labeled Pittsburg compound B ((17)O-PiB) as a molecular probe.
- Employed (17)O's unique coupling with hydroxyl protons for T2-weighted imaging.
- Applied JJVCPE imaging to visualize (17)O-PiB distribution in vivo.
Main Results:
- Successfully imaged (17)O-PiB in vivo using JJVCPE.
- Demonstrated the potential of (17)O JJVCPE imaging as a PET-like molecular MRI modality.
- Achieved in vivo visualization of beta-amyloid in transgenic mice.
Conclusions:
- This study presents the first successful in vivo ligand-based molecular MRI.
- It marks the first in vivo amyloid imaging using MRI.
- High-resolution, specific molecular MRI for clinical applications like senile plaque imaging is a future possibility.

