ABSTRACT
In an attempt to monitor µm-level trace constituents, we applied here (1)H-{(13)C-(15)N} triple-resonance nuclear magnetic resonance (NMR) to (13)C/(15)N-enriched l-Dopa as the inevitable precursor of the neurotransmitter dopamine in the brain. The perfect selectivity (to render endogenous components silent) and µm-level sensitivity (700â MHz spectrometer equipped with a cryogenic probe) of triple-resonance allowed the unambiguous and quantitative metabolic and pharmacokinetic analyses of administered l-Dopa/dopamine in the brain and liver of mice. The level of dopamine generated in the brain (within the range 7-76â µm, which covers the typical stimulated level of â¼30â µm) could be clearly monitored ex vivo, but was slightly short of the detection limit of a 7 T MR machine for small animals. This work suggests that µm-level trace constituents are potential targets of ex vivo monitoring as long as they contain N atom(s) and their appropriate (13)C/(15)N-enrichment is synthetically accessible.
ABSTRACT
Recently, we developed novel chiral dendrimer-triamine-coordinated Gd-MRI contrast agents (Gd-MRI CAs), which showed longitudinal relaxivity (r1) values about four times higher than that of clinically used Gd-DTPA (Magnevist(®), Bayer). In our continuing study of pharmacokinetic differences derived from both the chirality and generation of Gd-MRI CAs, we found that the ability of chiral dendrimer Gd-MRI CAs to circulate within the body can be directly evaluated by in vitro MRI (7 T). In this study, the association constants (K(a)) of chiral dendrimer Gd-MRI CAs to bovine serum albumin (BSA), measured and calculated with a quartz crystal microbalance (QCM) in vitro, were found to be an extremely easy means for evaluating the body-circulation ability of chiral dendrimer Gd-MRI CAs. The K(a) values of S-isomeric dendrimer Gd-MRI CAs were generally greater than those of R-isomeric dendrimer Gd-MRI CAs, which is consistent with the results of our previous MRI study in vivo.
Subject(s)
Contrast Media/chemistry , Contrast Media/pharmacokinetics , Dendrimers/chemistry , Gadolinium DTPA/chemistry , Magnetic Resonance Imaging/methods , Animals , Cattle , Cell Line , Mice , Polyamines/chemistry , Quartz Crystal Microbalance Techniques/methods , Serum Albumin, Bovine/chemistry , Tissue DistributionABSTRACT
Correction for 'Efficient singlet oxygen generation from sugar pendant C60 derivatives for photodynamic therapy' by Shigenobu Yano et al., Chem. Commun., 2015, DOI: 10.1039/c5cc07353g.
ABSTRACT
The amidation reaction between C60 with an activated ester group (1) and acetylated Glc (AcGlc) with an amino group (2) was performed to yield the target AcGlc-pendant C60 compound (3). The water soluble deacetylated compound, Glc-pendant C60 compound (4), exhibited high photocytotoxicity against HeLa cells due to the more efficient singlet oxygen generation as compared with that of Glc-pendant azafulleroids.
Subject(s)
Amides/chemistry , Fullerenes/chemistry , Glucose/chemistry , Photochemotherapy , Singlet Oxygen/chemistry , Acetylation , Cell Survival , HeLa Cells , Humans , Molecular StructureABSTRACT
A (13)C-enriched phosphorylcholine polymer ((13)C-PMPC) as a self-traceable MR (magnetic resonance) tag was conjugated with a fragment (scFv) of Herceptin, a clinical antibody against antigen Her2. When injected in model mice bearing Her2(+) (gastric) and Her2(-) (pancreatic) tumors, the antibody-tag conjugate (13)C-PMPC-scFv selectively accumulated in the Her2(+) tumor with a rapid build-up/decay (accumulation/clearance) profile and, with the use of the (1)H-(13)C double-resonance (heteronuclear correlation) technique, the Her2(+) gastric tumor was clearly MR imaged.
Subject(s)
Immunoconjugates/pharmacokinetics , Pancreatic Neoplasms/diagnosis , Stomach Neoplasms/diagnosis , Animals , Carbon Isotopes/pharmacokinetics , Cell Line, Tumor , Female , Humans , Immunoconjugates/chemistry , Magnetic Resonance Imaging , Mice , Mice, Inbred BALB C , Mice, Nude , Pancreatic Neoplasms/metabolism , Phosphorylcholine/analogs & derivatives , Phosphorylcholine/pharmacokinetics , Polymethacrylic Acids/pharmacokinetics , Receptor, ErbB-2/immunology , Receptor, ErbB-2/metabolism , Single-Chain Antibodies/pharmacokinetics , Stomach Neoplasms/metabolismABSTRACT
Polymers are concentration-amplified with respect to the monomeric units. We show here that a phosphorylcholine polymer enriched with (13)C/(15)N at the methyl groups is self-traceable by multiple-resonance (heteronuclear-correlation) NMR in tumor-bearing mice inoculated with the mouse rectal cancer cell line (colon 26). Preliminary measurements indicated that the present polymeric nanoprobe was satisfactorily distinguished from lipids and detectable with far sub-micromolar spectroscopic and far sub-millimolar imaging sensitivities. Detailed ex vivo and in vivo studies for the tumor-bearing mice administered the probe with a mean molecular weight of 63,000 and a mean size of 13 nm, revealed the following: (1) this probe accumulates in the tumor highly selectively (besides renal excretion) and efficiently (up to 30% of the injected dose), (2) the tumor can thus be clearly in vivo imaged, the lowest clearly imageable dose of the probe being 100 mg/kg or 2.0 mg/20-g mouse, and (3) the competition between renal excretion and tumor accumulation is size-controlled; that is, the larger (higher molecular-weight) and smaller (lower molecular-weight) portions of the probe undergo tumor accumulation and renal excretion, respectively. The observed size dependence suggests that the efficient tumor-targeting of the present probe is stimulated primarily by the so-called enhanced permeability and retention (EPR) effect, that is, size-allowed invasion of the probe into the tumor tissue via defective vascular wall. Self-traceable polymers thus open an important area of magnetic resonance imaging (MRI) of tumors and may provide a highly potential tool to visualize various delivery/localization processes using synthetic polymers.
Subject(s)
Colonic Neoplasms/diagnosis , Colonic Neoplasms/metabolism , Magnetic Resonance Imaging , Phosphorylcholine/chemistry , Phosphorylcholine/metabolism , Polymers/metabolism , Animals , Cell Line, Tumor , MiceABSTRACT
The synthesis, characterization, and functional evaluation of new size-controlled and biocompatible Gd(2) O(3) nanoparticles as a bimodal contrast agent for use in photoacoustic (PA) and magnetic resonance (MR) imaging are reported. These nanoparticles show a clear PA image by themselves, without conjugation with gold, rare earth metals, or dyes. Relaxivity measurement by MR imaging clearly shows that their relaxivity, r(1) , is twice that of clinically available Gd-DTPA.
Subject(s)
Biocompatible Materials , Gadolinium , Magnetic Resonance Imaging/methods , Microscopy, Fluorescence/methods , Nanoparticles/chemistry , Photoacoustic Techniques/methods , Animals , Biocompatible Materials/chemical synthesis , Contrast Media/chemical synthesis , Gadolinium/chemistry , Mice , Particle Size , Subtraction TechniqueABSTRACT
A novel rhodium-catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes to dienones and a novel synthesis of furans by an unusual cycloaddition of diaryl ketenes with internal alkynes have been developed. These reactions proceed smoothly with the same rhodium catalyst, RhCl(PPh(3))(3), and are highly dependent on the structure and reactivity of the starting ketenes.
Subject(s)
Alkynes/chemistry , Ethylenes/chemistry , Ketones/chemistry , Rhodium/chemistry , Catalysis , Molecular StructureABSTRACT
On the basis of the UV absorption spectra of the anti,cisoid alternating oligosilanes, the first experimental clear-cut evidence was presented for the generally accepted idea that the sigma conjugation in polysilanes does not effectively extend through a tetrasilane fragment with a small dihedral angle such as a cisoid turn.
