Ligand-Based Molecular MRI: O-17 JJVCPE Amyloid Imaging in Transgenic Mice

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.