89Zr Labeled Fe3O4@TiO2 Nanoparticles: In Vitro Afffinities with Breast and Prostate Cancer Cells

In this study, Fe₃O₄@TiO₂ nanoparticles were synthesized as a new Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) hybrid imaging agent and radiolabeled with ⁸⁹Zr. In addition, Fe₃O₄ nanoparticles were synthesized and radiolabeled with ⁸⁹Zr. Df-Bz-NCS was used as bifunctional ligand. The nanoconjugates were characterized with transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. Radiolabeling yields were 100%. Breast and prostate cancer cell affinities and cytotoxicity were determined using in vitro cell culture assays. The results demonstrated that Fe₃O₄@TiO₂ nanoparticles are promising for PET/MR imaging. Finally, unlike Fe₃O₄ nanoparticles, Fe₃O₄@TiO₂ nanoparticles showed a fluorescence spectrum at an excitation wavelength of 250 nm and an emission wavelength of 314 nm. Therefore, in addition to bearing the magnetic properties of Fe₃O₄ nanoparticles, Fe₃O₄@TiO₂ nanoparticles display fluorescence emission. This provides them with photodynamic therapy potential. Therefore multimodal treatment was performed with the combination of PDT and RT by using human prostate cancer cell line (PC3). The development of ⁸⁹Zr-Df-Bz-NCS-Fe₃O₄@TiO₂ nanoparticles as a new multifunctional PET/MRI agent with photodynamic therapy and hyperthermia therapeutic ability would be very useful.     

PHA-L lectin and carbohydrate relationship: conjugation with CdSe/CdS nanoparticles, radiolabeling and in vitro affinities on MCF-7 cells

This research aims to investigate the interaction between phytohemagglutinin-L (PHA-L) and sialic acid, which is abundant on the breast cancer cell (MCF-7) surface and displays monosaccharide characteristics, by experimental and computational methods. Experimentally, CdSe/CdS nanoparticles (QDs) were synthesized; PHA-L was conjugated with QDs and labeled with ¹²⁵I. Radiolabeling yield was found to be 97 ± 1.2 %. Afterwards, in vitro bioaffinities of radiolabeled PHA-L conjugated QDs have been investigated on MCF-7 cells and it has been observed that the cell incorporation increased with time. The results indicated that ¹²⁵I labeled QD-PHA-L conjugates represent significant affinity on MCF-7 cells. In the second step of the study, the crystal structure of carbohydrate interaction surface of PHA-L was extracted from the crystal structure of PHA-L. The interactions between this surface and sialic acid were calculated by computational tools. These calculations revealed specific interactions between PHA-L and sialic acid. Semi-empirical methods, PM3 and AM1, were used in these calculations. Significant outcomes have been obtained from the experimental and computational studies and these results demonstrated that PHA-L may be an effective agent for imagining MCF-7 cells.     

Synthesis,characterization and biodistribution of 99mTc-Bioquin-HMPAO (99mTc-BH) as a novel brain imaging agent

Recently, the development of novel brain imaging agents has aroused much interest thanks to limited number of brain cancer or diseases diagnosis agents. It is aimed to synthesize a novel brain imaging agent including a promise for further studies on AD diagnosis potential and investigate its bioaffinity with biodistribution studies on healthy Balb/c mice. A novel radiolabeled agent was synthesized and characterized. Quality control of ^99mTc-BH was performed utilizing solvent extraction and chromatographic (Radio TLC and Radio HPLC) methods. Bioaffinity of the ^99mTc-BH was investigated on male Balb/c mice at various time points (5, 30, 60, 120 min post-injection). Paper electrophoresis showed that ^99mTc-BH has a neutral structure. Radiochemical purity of ^99mTc-BH was over 95 % with appropriate stability for imaging period. Selected brain regions have uptakes over 4 % ID/g following intravenous injection. Hippocampus has uptake approximately 10 % ID/g. ^99mTc-BH has shown brain uptake, so it may prove to be valuable for brain imaging as a novel technetium-labeled agent. Further investigations with AD animal model are our on going effort to show that this agent has AD diagnosis potential.     

Interaction between green tea extract and 99mTc-pertechnetate on in vivo distribution

People drink various types of tea without knowing the side effects of biological and chemical contents and radiopharmaceutical interactions. In current study, it is aimed to evaluate the effects of green tea extract in different extraction solvents on the radiolabeling of the blood constituents with ^99mTc and on the biodistribution of radiopharmaceutical sodium pertechnetate (Na^99mTcO₄) in male Wistar Albino rats. The extraction of green tea was performed in different solvents. Biodistribution studies were performed on male rats which were treated via gavage with green tea extract in different extraction solvents or saline (0.9 % NaCl) as a control group for 7 days. The radiolabeling of blood constituents performed incubating with SnCl₂ and ^99mTc. According to experimental results, radiolabeling blood components with ^99mTc were not modified in the usage of the different extraction solvents for green tea extraction, but a significant alteration (P < 0.05) of biodistribution of Na^99mTcO₄ was observed after treatment with green tea extract in distilled water. Although there is no considerable effect on radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially with green tea extract in distilled water. The identified change monitored in this study may cause to reduce the risk of misdiagnosis and/or avoid the repetition of the examinations in nuclear medicine.     

A new agent for sentinel lymph node detection: preliminary results

Sentinel lymph node detection is widely used to identify lymph nodes that receive lymphatic drainage from a primary tumor. ^99mTc labeled iron oxide nanoparticles were prepared to invent a new colorful radioactive agent for sentinel lymph node detection. Iron oxide nanoparticles were produced by co-precipitation of FeCl₃ and FeCl₂ in the presence of NaOH. Then iron oxide nanoparticles were labeled with ^99mTc. ^99mTc labeled nanoparticles (7.4 MBq/0.1 mL) were intradermally injected in the distal hind limb of 16 rabbits. Dynamic and static lymphoscintigraphic images were taken for 24 h. Labeling efficiencies of ^99mTc-iron oxide nanoparticles were over 99%. Their sizes are between 50 and 60 nm. ^99mTc-iron oxide nanoparticles were accumulated in the popliteal lymph node in 11 of 16 rabbits (69%). Retention of nanoparticles in the popliteal lymph node was obvious at from 2nd through 24th hours. The radioactive lymph node was identified easily by gamma probe. The popliteal lymph node was excised and established for radioactivity and black dye. These black and radioactive nanoparticles may be potential agent successfully used for sentinel lymph node detection.     

Equilibrium and kinetic investigation of the interaction of model palladium(II) complex with biorelevant ligands

Pd(DME)Cl₂ complex was synthesized and characterized, where DME is 2‐{[2‐(dimethylamino)ethyl]‐methylamino}ethanol. Stoichiometry and stability constants of the complexes formed between various biologically relevant ligands (amino acids, peptides, DNA constituents, and dicarboxylic acids) and [Pd(DME)(H₂O)₂]²⁺ are investigated at 25°C and at constant 0.1 M ionic strength. The effect of dielectric constant of the medium on the stability constant of Pd(DME)‐CBDCA complex, where CBDCA is cyclobutanedicarboxylate, is also reported. The concentration distribution diagrams of the various species formed are evaluated. The kinetics of base hydrolysis of amino acid esters coordinated to Pd(DME)²⁺ complex is investigated. The effect of the temperature on the kinetics of base hydrolysis of glycine methyl ester complex is studied. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 608–618, 2010     

Imaging of bacterial infection with 99mTc-labeled HBD-1

The aim of this study was to evaluate ^99mTc labeled human β-defensin-1 (HBD-1) for discrimination between bacterial infection and sterile inflammation. For this purpose, HBD-1 was radiolabeled with ^99mTc and its in vivo distribution was evaluated in inflamed rats with Staphylococcus aureus (S. aureus) and sterile inflamed rats with turpentine oil. After injection into inflamed and sterile inflamed rats, ^99mTc-HBD-1 was rapidly removed from the circulation via the kidneys. Binding of ^99mTc-HBD-1 to inflamed muscle (T/NT = 20 at 120 min) was two times higher than binding to sterile inflamed muscle (T/NT = 10 at 120 min) of rats. It was demonstrated that ^99mTc-HBD-1 can be used to detect S. aureus inflammation in rats. However, the radiolabeled antimicrobial peptide showed only poor uptake in sterile inflammation with turpentine oil in rats. As a result, ^99mTc-HBD-1 can be useful for detection of bacterial inflammation.     

Preparation,quality control and stability of <Superscript>99m</Superscript>Tc-cefuroxime axetil

Cefuroxime axetil, a cephalosporin antibiotic used to treat bacterial infections, was investigated to label with ^99mTc. Radiolabeling of cefuroxime axetil was carried out by using stannous chloride method. Effects of pH and stannous chloride amount on the radiolabeling yield were investigated. The radiochemical purity of ^99mTc-cefuroxime axetil was determined by thin layer radio chromatography (TLRC), electrophoresis and high performance liquid chromatography. The maximum radiolabeling yield was 98±1%.     

Potentiometric and antimicrobial studies on the asymmetric Schiff bases and their binuclear Ni(II) and Fe(III) complexes; synthesis and characterization of the complexes

The protonation constants of two nitro-Schiff bases SB¹, SB² and three asymmetric tetradentate diimines H₂L¹, H₂L² and H₂L³ and the stability constants of their ML type binuclear Ni(II) and Fe(III) complexes have been determined potentiometrically. The asymmetric diimines are (2OH) RCHNC₆H₄CHNR′ (2OH) type compounds [where R = R′ = phenyl for H₂L¹; R = naphthyl, R′ = phenyl for H₂L² and R = R′ = naphthyl for H₂L³]. The effect of tautomeric forms on the acid-base properties of the diimines has been investigated and discussed. In addition, dimeric and binuclear Ni(II) and Fe(III) complexes of the diimines have been synthesized and characterized by physical and spectroscopic techniques. Also, in vitro antimicrobial activities of the diimines and the complexes have been evaluated against three bacteria: Micrococcus luteus (NRLL B-4375), Bacillus cereus (RSKK 863), Escherichia coli (ATCC 11230) and the fungus: Candida albicans (ATCC 10239).     

In vivo radioprotective effects of Nigella sativa L oil and reduced glutathione against irradiation-induced oxidative injury and number of peripheral blood lymphocytes in rats

Radiotherapy is one of the most common therapies for treating human cancers. Several studies have indicated that irradiation induces reactive oxygen species (ROS), which play an important role in radiation damage of the cell. It has been shown that Nigella sativa L. (NS) and reduced glutathione (GSH) have both an antiperoxidative effect on different tissues and a scavenger effect on ROS. The purpose of this study was to determine the antioxidant and radio-protective roles of NS and GSH against irradiation-induced oxidative injury in an experimental model. The NS group was administrated NS (1 mL/kg body weight), the GSH group was injected GSH (150 mg/kg body weight) and the control group was given physiologic saline solution (1 mL/kg body weight) for 30 consecutive days before exposure to a single dose of 6 Gy of radiation. Animals were sacrificed after irradiation. Malondialdehyde, nitrate, nitrite (oxidative stress markers) and ascorbic acid, retinol, beta-carotene, GSH and ceruloplasmin (nonenzymatic antioxidant markers) levels and peripheral blood lymphocytes were measured in all groups. There were statistically significant differences between the groups for all parameters (P < 0.05). Whole-body irradiation caused a significant increase in blood malondialdehyde, nitrate and nitrite levels. The blood oxidative stress marker levels in irradiated rats that were pretreated with NS and GSH were significantly decreased; however, non-enzymatic antioxidant levels were significantly increased. Also, our results suggest that NS and GSH administration prior to irradiation prevent the number of alpha-naphthyl acetate esterase peripheral blood T lymphocytes from declining. These results clearly show that NS and GSH treatment significantly antagonize the effects of radiation. Therefore, NS and GSH may be a beneficial agent in protection against ionizing radiation-related tissue injury.