title: Self-organized Mn2+-Block Copolymer Complexes and Their Use forIn VivoMR Imaging of Biological Processes.
abstract: Manganese-block copolymer complexes (MnBCs) that contain paramagnetic Mn ions complexed with ionic-nonionic poly(ethylene oxide-b-poly(methacrylate) have been developed for use as a T1-weighted MRI contrast agent. By encasing Mn ion within ionized polymer matrices, r1 values could be increased by 250-350 % in comparison with free Mn ion at relative high fields of 4.7 to 11.7 T. MnBCs were further manipulated by treatment with NaOH to achieve more stable complexes (iMnBCs). iMnBCs delayed release of Mn2+which could be accelerated by low pH, indeed by cellular uptake via endocytosis into acidic compartments. Both complexes exhibited good T1 contrast signal enhancement in liver following intravenous infusion. The contrast was observed in gallbladder due to the clearance of Mn ion from liver to biliary process. iMnBCs, notably, showed a delayed contrast enhancement profile in gallbladder, which was interpreted to be due to degradation and excretion of Mn2+ions into the gallbladder. Intracortical injection of iMnBCs into the rat brain also led to delayed neuronal transport to thalamus. The delayed enhancement feature may have benefits for targeting MRI contrast to specific cells and surface receptors that are known to be internalized by endocytosis.
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Nikorn
authors.initials: N
authors.lastname: Pothayee
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Der-Yow
authors.initials: DY
authors.lastname: Chen
authors.affiliation: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Aronova
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Chunqi
authors.initials: C
authors.lastname: Qian
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bouraoud
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dodd
authors.affiliation: Laboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Leapman
authors.affiliation: Laboratory of Functional and Molecular Imaging, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Koretsky