<Superscript>99m</Superscript>Tc-exorphin C: A new peptide radiopharmaceutical for tumor imaging

Summary The aim of this study was to label exorphin C with ^99mTc and to examine its usefulness as opioid receptor binding radiopharmaceutical in Albino Wistar rats. Exorphin C, which is a peptide with 5 aminoacids, was labeled with ^99mTc using glucoheptonate (GH) as a bifunctional chelating agent. Labeling efficiency was higher than 98%. The compound was stable for at least 5 hours at room temperature. Mammary tumor bearing Albino Wistar rats were imaged using gamma-camera. Biodistribution studies were also performed. Results demonstrated that ^99mTc-glucoheptonate-exorphin C (^99mTc-GE) analogs may be useful as a new class of receptor-binding peptides for the diagnosis and therapy of some cancer diseases related with opioid receptor-expressing tissues.     

Synthesis of a 99mTc labeled estrogen-derivative and the determination of its radiopharmaceutical potential on rats

An estrogen derivative 1-(3, 17-α-estradiolyl propin-1-yl-3-(1,4,8,11-tetraazacyclotetradecyl)-propanate (ESTACPA) was synthesized. The product was purified by HPLC and characterized by NMR and IR spectroscopy. The synthesized compound was labeled with ^99mTc. The biodistribution studies were performed on female Albino Wistar rats. The rats were sacrificed and their organs were removed. The radioactivities of the organs were counted using a gamma-counter. The activity per gram tissue was calculated and time versus activity curves were generated. The ^99mTc-ESTACPA uptake by the uterus and ovary such as ER-rich tissues, were observed. The pancreas and stomach also showed a significant uptake. This revised version was published online in July 2006 with corrections to the Cover Date.     

Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative: ethyl-morphine glucuronide (em-glu)

In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with ¹³¹I using iodogen method. The quality control studies of radiolabeled compound (¹³¹I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of ¹³¹I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that ¹³¹I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats’ brains.     

A New Approach for in vitro Imaging of Breast Cancer Cells by Anti‐Metadherin Targeted PVA‐Pyrene

Poly(vinyl alcohol)‐pyrene‐anti‐metadherin (PVA‐Py‐(Anti‐MTDH)), a novel antibody based water soluble probe containing both fluorescent and target sites in the structure for in vitro imaging of breast cancer cells is reported here. Since breast cancer cells have an excess of MDTH protein expressed on the surface, a PVA‐Py prepared by “Click chemistry” approach is targeted by Anti‐MTDH antibody and applied to the MCF‐7 cell line. After characterization, the designed architecture was evaluated in terms of cell incorporation efficiency and compared with a non‐targeted structure (PVA‐Py). Atomic force microscopy (AFM) and fluorescence microscopy images of cells after incubation of the probe molecules were also obtained to monitor the interaction of the probes with the cancerous cells.

     

Development of a micro-total analysis system (μ-TAS) for the determination of catecholamines

In this study, the first micro-total analysis system (μ-TAS) for catecholamines (dopamine, epinephrine, and norepinephrine) analysis in which preconcentration, separation, and determination steps were integrated on a microchip was developed. Electrophoresis microchips in a variety of channel lengths and designs were produced in borofloat glass for the μ-TAS studies. Chambers for the preparation of monolithic disks were formed in the microchips at the intersection of the injection and separation channels. Vinyl phenylboronic acid–ethylene glycol dimethacrylate polymers were prepared as monolithic disks in these chambers with a depth of 0.05 mm and a diameter of 2.1 mm. The microchips could be used more than 50 times if mechanical problems such as plugging or fracturing did not occur. Adsorption and elution of catecholamines were realized electrokinetically, with catecholamines determined via laser-induced native fluorescence detection following elution and electrophoretic separation. The most promising results were obtained with 100 mM phosphate buffer (pH 2) for elution with 25% propanol added to the separation buffer (100 mM phosphate, pH 3).     

Chemical constituents of two sages with free radical scavenging activity

From the aerial parts of Salvia trichoclada Bentham and S. verticillata L. one new and two known phenolic acids, 3-(3',4'-dihydroxyphenyl)-2-hydroxymethyl propionic acid (1), 3-(3',4'-dihydroxyphenyl) lactic acid (2), and rosmarinic acid (3); two flavonoids, apigenin 4'-methyl ether 7-O-glucuronide (4), and luteolin 7-O-beta glucuronide (5); two lupan type triterpene aglycones, lupeol (6), and 30-hydroxylup-20 (29)-en-3-on (7); an oleanane-type triterpene acid, oleanolic acid (8); and an ursan-type triterpene acid, ursolic acid (9) were isolated. The structures of the compounds were elucidated by spectroscopic analysis. Different extracts of the plants were examined for their free radical scavenging activities by DPPH (2,2-Diphenyl-1-picrylhydrazyl) assay. Some of the polar extracts showed high free radical scavenging activity.     

Diethylstilbestrol glucuronide (DESG): synthesis, labeling with radioiodine and in vivo/in vitro evaluations

Diethylstilbestrol (DES) is a synthetic non-steroidal estrogen, pharmacologic effects of which resemble natural estrons; today it is being used to treat some types of postmenopausal breast cancer and advanced prostate cancer. The aim of current study is conjugation of glucuronic acid (G) to DES and to evaluate radiopharmaceutical potential of this estrogen glucuronide derivative (DESG) which is specific to β glucuronidase enzyme consisting tumor cells. Taking into consideration the compatibility to the chemical structures of the synthesized product, ¹³¹I and ¹²⁵I were chosen as the appropriate radionuclides and DESG was labeled with these radionuclides utilizing iodogen method. The radiochemical yields of ^125/131I-DESG were over 90 % according to thin layer radio chromatography method. The biodistribution of ¹³¹I-DESG in healthy female Wistar Albino rats has been investigated and the range of the breast/blood and breast/muscle ratios were approximately 2 and 13 in 240 min for ER unsaturated studies. Effects of the radioiodinated DES and DESG on the cells were examined using MCF-7, A-549, Caco-2 cell lines. ¹²⁵I-DESG has higher incorporation percentages than ¹²⁵I-DES on MCF-7 cells. The radioiodinated DESG has the desired radiopharmaceutical properties which could be candidate radiopharmaceuticals for diagnosis and especially radionuclide therapy of breast tumors.     

Microchip extraction of catecholamines using a boronic acid functional affinity monolith

A novel solid phase extraction microchip with a boronic acid functional affinity monolithic disc was developed in this work. Vinyl phenylboronic acid–ethylene glycol dimethacrylate co-polymer monoliths, which have pore sizes up to 20 μm, were investigated for extraction of catecholamines using adsorption and desorption studies in a batch system. Desorption yields of greater than 90% were achieved for catecholamines at pH 3 and below. Monolithic discs were then formed in chambers in borofloat glass microfluidic chips using in situ UV polymerization. Adsorption on the monolithic discs was performed via electrokinetic flow, with catecholamines determined via laser-induced native fluorescence (LINF) detection following electrokinetic elution. Microchips containing the boronic acid functional polymer discs worked well for extraction of catecholamines, providing greater than 100 fold concentration enrichment. This study demonstrated that a solid phase extraction microchip, containing an easily prepared monolith disc, will be useful for boronate affinity extraction of cis-diol containing compounds.     

Anti-hepatocellular carcinoma,antioxidant, anti-inflammation and antimicrobial investigation of some novel first and second transition metal complexes

New coordination compounds of some selected metal ions from the first and second transition metals series with a Schiff base were synthesized and characterized. The Schiff base is derived from 4-Aminoantipyrine and 3-(hydroxyimino) butan-2-one. The compounds were characterized by different analysis tools like; elemental analysis, mass spectra, Fourier transform infrared (FTIR) as well as electronic spectra, magnetic measurements, molar conductance and thermal analysis technique. All complexes were formed with 1:1 (metal: ligand) stoichiometry except Mn (II) where 1:2 (Mn: ligand) is formed. Schiff base ligand interacted as a tridentate ligand by using the nitrogen atoms of the imine and the oximato groups and the carbonyl oxygen atom as donor groups with all studied metal ions except copper (II) and manganese (II) where the carbonyl oxygen is not shared in the coordination. These complexes show various physicochemical properties. X-ray powder diffraction shows different crystal systems; Cd (II) complex: hexagonal, Cu (II) complex: orthorhombic; and [Ni (II), Mn (II), Rh (III) & Pd (II)] complexes: monoclinic. All compounds showed potent cytotoxicity against the growth of human liver cancer cell lines. The square planar Pd (II) complex was more active than those of octahedral geometries of all other synthesized complexes. Cd (II) complex has the highest microbial growth inhibition than the rest of the prepared complexes. The docking active sites interactions were evaluated using the selected proteins EGFR tyrosine kinase and protein crystal structure of GlcN-O-P synthase. in vitro antioxidant assay revealed potent free radical scavenging activity of the three synthesized Cu (II), Pd (II) and Rh (III) complexes that exceeded the standard ascorbic acid. Pd (II) complex shows the most significant inhibition denaturation percent.     

Preparation and characterization of radiolabeled magnetic nanoparticles as an imaging agent

The degradation of crystal violet in aqueous solution was investigated using kaolin-supported zero-valent iron nanoparticles (K-nZVI). It was found that K-nZVI with a ratio of kaolin:zero-valent iron nanoparticles (nZVI) at 1:1 was most effective in removing crystal violet. Batch experiments show that more than 97.29?% crystal violet was degraded using K-nZVI, while only 24.36?% was removed using nZVI after reacting for 7?min, where the solution contained 100?mg?L^?1 crystal violet at pH 6.5. This is due to a decrease in aggregation of Fe⁰ nanoparticles and enhanced their reactivity in the presence of kaolin, which was confirmed by the characterization using scanning electron microscopy. X-ray diffraction shows the formation of iron oxide and hydroxide, while UV?CVis spectral shows that the absorption peak of crystal violet was reduced, as well as Fourier transform infrared shows that new bands were formed after K-nZVI reacting with crystal violet. These suggest that degradation of crystal violet by K-nZVI include the oxidation of iron, the adsorption of crystal violet onto the K-nZVI, the transformation of crystal violet to leuko-crystal violet, and finally the cleavage of C=C bond.