The role of imaging is crucial for the surveillance, diagnosis, staging and treatment monitoring of hepatocellular carcinoma (HCC). Over the past few years, considerable technical advances were made in imaging of HCCs. New imaging technology, however, has introduced new challenges in our clinical practice. In this article, the current status of clinical imaging techniques for HCC is addressed. The diagnostic performance of imaging techniques in the context of recent clinical guidelines is also presented.
Carcinoma, Hepatocellular/*diagnosis/radiography/ultrasonography ; Contrast Media/chemistry ; Ferric Compounds/chemistry ; Humans ; Iron/chemistry ; Liver Neoplasms/*diagnosis/radiography/ultrasonography ; Magnetic Resonance Imaging ; Meglumine/analogs & derivatives/chemistry ; Organometallic Compounds/chemistry ; Oxides/chemistry ; Tomography, X-Ray Computed

Urokinase plasminogen activator receptor (uPAR) is a membrane protein which is attached to the cellular external membrane. The uPAR expression can be observed both in tumor cells and in tumor-associated stromal cells. Thus, in the present study, the human amino-terminal fragment (hATF), as a targeting element to uPAR, is used to conjugate to the surface of superparamagnetic iron nanoparticle (SPIO). Flowcytometry was used to examine the uPAR expression in different tumor cell lines. The specificity of hATF-SPIO was verified by Prussian blue stain and cell phantom test. The imaging properties of hATF-SPIO were confirmed in vivo magnetic resonance imaging (MRI) of uPAR-elevated colon tumor. Finally, the distribution of hATF-SPIO in tumor tissue was confirmed by pathological staining. Results showed that the three cells in which we screened, presented different expression characteristics, i. e., Hela cells strongly expressed uPAR, HT29 cells moderately expressed uPAR, but Lovo cells didn't express uPAR. In vitro, after incubating with Hela cells, hATF-SPIO could specifically combined to and be subsequently internalized by uPAR positive cells, which could be observed via Prussian blue staining. Meanwhile T2WI signal intensity of Hela cells, after incubation with targeted probe, significantly decreased, and otherwise no obvious changes in Lovo cells both by Prussian blue staining and MRI scans. In vivo, hATF-SPIO could be systematically delivered to HT29 xenograft and accumulated in the tumor tissue which was confirmed by Prussian Blue stain compared to Lovo xenografts. Twenty-four hours after injection of targeting probe, the signal intensity of HT29 xenografts was lower than Lovo ones which was statistically significant. This targeting nanoparticles enabled not only in vitro specifically combining to uPAR positive cells but also in vivo imaging of uPAR moderately elevated colon cancer lesions.
Cell Line, Tumor ; Colonic Neoplasms ; diagnosis ; Ferric Compounds ; Humans ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; chemistry ; Molecular Imaging ; methods ; Receptors, Urokinase Plasminogen Activator ; chemistry ; Staining and Labeling

OBJECTIVETo evaluate the effect of Fe2O3 and CeO2 as colorants on yttria stabilized tetragonal zirconia poly-crystals (Y-TZP) powder.

METHODSThe spray granulation slurry of colored zirconia was prepared with different concentrations of Fe2O3 (0.15%) and CeO2 (4%), which were added in Y-TZP. Zirconia powder was made by spray granulation. The powder specimens were divided into three groups: uncolored zirconia, Fe2O3 (0.15%) zirconia, and CeO2 (4%) zirconia. The particle morphologies of the powder specimens were measured with a laser particle size analyzer and an optical microscope.

RESULTSThe differences in D50 among the three groups were statistically significant (P<0.05). Group Fe2O3 showed a significant difference from groups CeO2 and uncolored zirconia (P<0.05). Group uncolored zirconia showed no significant difference from group CeO2 (P>0.05). Mostly spherical powder was observed in the three groups.

CONCLUSIONFe2O3 as a colorant can affect particles, whereas CeO2 has no effect.

Color ; Dental Stress Analysis ; Ferric Compounds ; Humans ; Materials Testing ; Yttrium ; chemistry ; Zirconium ; chemistry

OBJECTIVE: To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. MATERIALS AND METHODS: The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin(R))-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. RESULTS: We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. CONCLUSION: Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.
3T3 Cells ; Animals ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/chemistry/*drug therapy ; Cell Line, Tumor ; Drug Delivery Systems/methods ; Female ; Ferric Compounds/chemistry ; Humans ; Liposomes ; Magnetite Nanoparticles/administration & dosage/*chemistry ; Mice ; Molecular Targeted Therapy/methods ; Nanoconjugates/administration & dosage/*chemistry ; Nanoparticles/chemistry ; *Receptor, erbB-2/immunology ; Silicon Dioxide/administration & dosage/*chemical synthesis/chemistry

Bio-active components from Carthamus tinctorius were separated on the basis of antioxidant capacities in vitro. The antioxidant capacity was investigated on the basis of the ability to scavenge DPPH radical, ABTS radical and reduce Fe3+ of different polar fractions. Furthermore, the chemical compounds were isolated from bio-active fraction, and were evaluated for the antioxidative effects. Five major components were isolated and identified from water extract as 6-hydroxykaempferol 3,6,7-tri-O-β-D-glucoside(1), 6-hydroxykaempferol 3-O-β-rutinoside-6-O-β-D-glucoside (2), 6-hydroxykaempferol 3-O-β-D-glucoside (3), hydroxysafflor yellow A (4) and anhydrosafflor yellow B (5). By evaluating and comparing the antioxidative effects of different fractions and obtained compounds, the results showed that water extract displayed significantly high antioxidative activities and 6-hydroxykaempferol glycosides and quinochalcone C-glycosides were found as main contribution for antioxidant property.
Antioxidants ; isolation & purification ; metabolism ; pharmacology ; Benzothiazoles ; metabolism ; Biphenyl Compounds ; metabolism ; Carthamus tinctorius ; chemistry ; Chalcone ; analogs & derivatives ; isolation & purification ; metabolism ; pharmacology ; Ferric Compounds ; metabolism ; Free Radicals ; metabolism ; Kaempferols ; isolation & purification ; metabolism ; pharmacology ; Oxidation-Reduction ; drug effects ; Picrates ; metabolism ; Plant Extracts ; isolation & purification ; metabolism ; pharmacology ; Plants, Medicinal ; chemistry ; Quinones ; isolation & purification ; metabolism ; pharmacology ; Sulfonic Acids ; metabolism ; Water ; chemistry

OBJECTIVETo evaluate the role of 2-deoxy-D-glucose (2-DG) modified supermagnetic iron oxide nanoparticles (SPIO) (γ-Fe2O3@DMSA-DG NPs) in tumor detection as a magnetic resonance imaging (MRI) contrast agent.

METHODSγ-Fe2O3@DMSA-DG NPs was prepared. The degree of A549 cells targeted absorption of γ-Fe2O3@DMSA-DG NPs was detected by Prussian blue staining, colorimetric assay, T2W and multi-echo sequence MRI. γ-Fe2O3@DMSA NPs was used as a control agent, and free D-glucose as a competitive inhibitor. Human lung adenocarcinoma A549 xenograft tumor was prepared in nude mice. Sterile aqueous suspension of γ-Fe2O3@DMSA NPs or γ-Fe2O3@DMSA-DG NPs was injected into the tail vein of nude mice. Before and 6, 12, 24, 48 h after injection, MRI imaging of the mice was performed. T2 signal intensity of the tumor, brain, liver and thigh skeletal muscles, and T2 values of the tumors were measured.

RESULTSThe average diameter of the particles was about 10 nm, and there were no significant differences between the diameters of γ-Fe2O3@DMSA NPs and γ- Fe2O3@DMSA-DG NPs. The IR spectra showed the C-N retractable vibration peak at γ-Fe2O3@DMSA-DG NPs surface, indicating that 2-DG was conjugated to the γ-Fe2O3@DMSA NPs. The Prussian blue staining, colorimetric assay, MRI T2 signal intensity and T2 values revealed that γ-Fe2O3@DMSA-DG NPs were significantly more absorbed by A549 cells at growth peak than γ-Fe2O3@DMSA NPs, and the absorption of γ-Fe2O3@DMSA-DG NP was inhibited by free D-glucose. The results of in vivo examination showed that before and at 6, 12, 24, 48 h after injection of γ-Fe2O3@DMSA-DG NPs, the mean T2 signal intensities of the tumors were (326.00 ± 16.26)s, (276.40 ± 5.13)s, (268.40 ± 30.58)s, (240.40 ± 25.93)s, (262.20 ± 30.04)s, respectively, and the T2 values of the tumors were (735.80 ± 20.93) ms, (645.80 ± 69.58) ms, (615.00 ± 124.61) ms, (570.60 ± 67.78) ms, and (537.80 ± 105.29) ms, respectively. However, before and at 6, 12, 24, 48 h after injection of γ-Fe2O3@DMSA NPs, the mean T2 signal intensities of the tumors were (335.60 ± 4.93)s, (290.80 ± 5.93)s, (273.40 ± 15.08)s, (327.40 ± 16.65)s, and (313.20 ± 20.45)s, respectively, and T2 values were (686.00 ± 21.44)ms, (617.80 ± 69.93)ms, (645.20 ± 85.89)ms, (669.40 ± 13.72)ms, and (608.80 ± 61.90)ms, respectively. The T2 signal intensity and T2 value of the tumors were not declined generally after injection. The liver T2 signal intensity was decreased after injection of both γ-Fe2O3@DMSA-DG NPs and γ-Fe2O3@DMSA NPs, and T2 signal intensity of the brain and muscle did not show significant changes.

CONCLUSIONSγ-Fe2O3@DMSA-DG NPs has an ability to target glucose receptors overexpressed in tumors, and may serve as a MRI contrast agent for tumor detection.

Adenocarcinoma ; diagnosis ; metabolism ; pathology ; Animals ; Cell Line, Tumor ; Colorimetry ; Contrast Media ; chemistry ; pharmacokinetics ; Deoxyglucose ; chemistry ; pharmacokinetics ; Ferric Compounds ; chemistry ; pharmacokinetics ; Humans ; Image Enhancement ; Lung Neoplasms ; diagnosis ; metabolism ; pathology ; Magnetic Resonance Imaging ; Magnetite Nanoparticles ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Transplantation ; Particle Size

Aqueous dispersion and stability of Fe3O4 nanoparticles remain an issue unresolved since aggregation of naked iron nanoparticles in water. In this study, we successfully synthesized different Fe3O4 super-paramagnetic nanoparticles which were modified by three kinds of materials [DSPE-MPEG2000, TiO2 and poly acrylic acid (PAA)] and further detected their characteristics. Transmission electron microscopy (TEM) clearly showed sizes and morphology of the four kinds of nanoparticles. X-ray diffraction (XRD) proved successfully coating of the three kinds of nanoparticles and their structures were maintained. Vibrating sample magnetometer (VSM) verified that their magnetic properties fitted for the super-paramagnetic function. More importantly, the particle size analysis indicated that Fe3O4@PAA had a better size distribution, biocompatibility, stability and dispersion than the other two kinds of nanoparticles. In addition, using CNE2 cells as a model, we found that all nanoparticles were nontoxic. Taken together, our data suggest that Fe3O4@PAA nanoaparticles are superior in the application of biomedical field among the four kinds of Fe3O4 nanoparticles in the future.
Ferric Compounds ; chemistry ; Magnetite Nanoparticles ; chemistry ; Microscopy, Electron, Transmission ; Spectroscopy, Fourier Transform Infrared ; Surface Properties ; Water ; chemistry ; X-Ray Diffraction

This paper provides a brief overview of the current research activities which focused on the bio-application of gold magnetic nanocomposite particles. By combining the magnetic characteristics of the iron oxide core with the unique features of nano-gold particles such as targeting by surface modification and optical properties, such composite nanoparticles have a wide range of applications in cancer hyperthermia, CT and MRI imaging, bio-separation, bio sensors, gene diagnosis, drug targeting and many other biomedical fields.
Diagnostic Imaging ; Drug Delivery Systems ; Ferric Compounds ; chemistry ; Gold ; chemistry ; Humans ; Magnetics ; Nanocomposites ; chemistry ; Nanoparticles ; chemistry ; Neoplasms

OBJECTIVETo prepare matrine double-sensitive colon-specific pellets and study the factors affecting its quality and evaluateing the colon-specific effects of preparation.

METHODMatrine enzyme-sensitive pellets core were prepared by carboxymethyl konjac glucomannan as the main carrier material, and coated the core by acrylic resin II and III to prepare matrine double-sensitive colon-specific pellets. The prescription and technology of the matrine colon-specific pellets were studied by the single factor investigation, through the in vitro release test and coating rate determination.

RESULTThe optimized process conditions: FeCl3 concentration is 4.0 g x L(-1), chitosan concentration is 3.0 g x L(-1), carboxymethyl konjac glucomannan concentration is 20 g x L(-1), mixed gel solution pH value is 3. The release of matrine is less than 30% in the simulation of the upper gastrointestinal medium. The release of matrine is close to 100% in simulated full gastrointestinal medium, the coating weight is 7%.

CONCLUSIONThe prepared pellets have good colon positioning effect in vitro.

Acrylic Resins ; chemistry ; Administration, Oral ; Alkaloids ; administration & dosage ; chemistry ; pharmacokinetics ; Chitosan ; chemistry ; Chlorides ; chemistry ; Colon ; metabolism ; Delayed-Action Preparations ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Ferric Compounds ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Mannans ; chemistry ; Quinolizines ; administration & dosage ; chemistry ; pharmacokinetics ; Reproducibility of Results ; Tablets, Enteric-Coated ; Time Factors

OBJECTIVETo explore the feasibility of magnetic resonance cell imaging technology by using polyethylene imine (PEI)-coated magnetic nanoparticles of Fe₄O₄ (PEI-Fe₄O₄-MNPs) to track cell biology behavior.

METHODSEndocytic PEI-Fe₄O₄-MNPs in SHI-1 cells were observed by transmission electron microscopy (TEM) . Iron contents of nano-labeled cells were analyzed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES) and Prussian blue staining. The proliferation ability of labeled cells was detected by cell counting kit-8 (CCK-8) assay; the differentiation and colony-forming abilities were also observed. SHI-1 cells without endocytosing PEI-Fe₄O₄-MNPs were used as control.

RESULTSOur data showed that PEI-Fe₄O₄-MNPs could label SHI-1 cells. The labeling efficiency depended on the nanoparticles' concentration and the duration of cells treating. Inhibition rates of SHI-1cells labeled by 60-100 μg Fe/ml PEI-Fe₄O₄-MNPs were much higher than of 5-50 μg Fe/ml ones following treating by 5-100 μg Fe/ml PEI-Fe₄O₄-MNPs for 48 hrs. The expressions of CD11b and CD14 were (78.4±18.5)% and (18.7±2.9)% in control vs (83.3±14.2)% and (20.4±2.1)% in cells fractions treated by 30 μg Fe/ml PEI-Fe₄O₄-MNPs. Clony-forming rates of SHI-1 cells labeled by 0, 20 , 50 μg Fe/ml PEI-Fe₄O₄-MNPs were (25.20±7.22)%, (25.93±13.15)%, (23.37±9.33)%, respectively. Differentiation and colony-forming potentials of labeled cells were similar with control in the certain range of PEI-Fe₄O₄-MNPs concentration.

CONCLUSIONSHI-1 cells were efficiently labeled by PEI-Fe₄O₄-MNPs with well biocompatibilities in proper range of concentration, the latter could be coupled with magnetic resonance imaging (MRI) to track cells in vivo.

Cell Line, Tumor ; Coated Materials, Biocompatible ; chemistry ; Ferric Compounds ; chemistry ; Humans ; Magnetic Resonance Imaging ; Magnetics ; Microscopy, Electron, Transmission ; Nanoparticles ; chemistry ; Polyethyleneimine ; chemistry