Tropolone,a ligand for a lipophilic chelate with technetium-99m

A lipophilic chelate formed from tropolone and^99mTc is described. Radiochemical yields of the chelate were 90–95%. The radiochemical purity of neutral chelate as determined by HPLC was greater than 95%. The octanol/water partition coefficient of the chelate was 3.2 Whole-body distribution studies of the labeled chelate were carried out in rats.     

Preparation,characterization and biodistribution of salicylidene- and pyridoxylidene-thyroxine complexes of technetium-99m

New Schiff bases, salicylidene- and pyridoxylidene-thyroxine have been prepared and characterized. They were labeled with^99mTc. The labeling yield of the Schiff bases was over 95%. About 60% of the activity was bound to -globulin and albumin fractions when the labled compounds were incubated with a serum sample. The labeled compounds, after i.v. administration to rats, rapidly cleared from blood and excreted into the small intestine. They appeared to behave as hepatobiliary agents.     

Synthesis, radiochemistry and stability of the conjugates of technetium-99m complexes with Substance P

Two types of technetium-99m complexes: (i) with the Hynic ligand linked to Substance P(1–11) and (ii) of the type ‘4 + 1’ consisting of tetradentate tripodal chelator tris(2-mercaptoethyl)-amine and monodentate isocyanide ligand previously coupled with Substance P(1–11), have been prepared on the n.c.a. scale. The obtained conjugates exhibit different lipophilicity and high stability in neutral aqueous solutions, even in the presence of excess concentration of histidine/cysteine competitive standard ligands. The conjugate (^99mTc(NS₃)(CN))₂–SP containing two technetium-99m species in the molecule may be expected to be an extremely good diagnostic radiopharmaceutical.     

Characterization of technetium-99m complexes of pentane-2,4-dione bis(N-methylthiosemicarbazone)

Further characterization of the two neutral technetium-99m (99mTc) complexes of pentane-2,4-dione bis-(N-methylthiosemicarbazone) (PETS) was carried out using a new dianionic PETS derivative, 3,3-dimethyl-pentane-2,4-dione bis(N-methylthiosemicarbazone) (DM-PETS), and the well characterized 99mTc complex of 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (DADT) as references. While PETS generated two neutral 99mTc complexes, 99mTc-PETS-L1 and 99mTc-PETS-L2, by both the stannous reduction method and the ligand exchange reaction with six-coordinated 99mTc(V) complex of N,N'-ethylenebis(acetylacetone imine), DM-PETS formed only one neutral 99mTc complex. 99mTc-PETS-L2, the more lipophilic complex of the two 99mTc-PETS, was obtained with a much higher yield than 99mTc-PETS-L1 by the ligand exchange reaction of PETS with the five-coordinated 99mTc(V) complex of glucoheptonate. In addition, while 99mTc-PETS-L2 and 99mTc-DADT remained unchanged in the presence of CN- anions, a breakdown of the original complexes was observed in 99mTc-PETS-L1 and 99mTc-DM-PETS. All four 99mTc complexes exhibited similar brain, heart and pancreas extraction when injected into mice. These cumulative results imply that 99mTc-PETS-L1 and 99mTc-DM-PETS are six-coordinated mononuclear 99mTc(V) complexes and that 99mTc-PETS-L2 is a five-coordinated mononuclear 99mTc(V) complex. These results also suggest that while the chelate ring structure of the 99mTc-dithiosemicarbazone (DTS) chelate played a significant role in its stability, ionization of the third proton of the PETS molecule and the subsequent resonating structure afforded further stability to the 99mTc-PETS complex. Markedly high lipophilicity of the 99mTc-PETS-L2 may also be explained by assuming that 99mTc-PETS-L2 is the five-coordinated resonating structure.     

Preparation of new technetium-99m NNS/X complexes and selection for brain imaging agent

Quantification of regional cerebral blood flow(rCBF) plays an important role in the diagnosis ofvarious cerebrovascular and neurological diseases. Innuclear medicine, brain perfusion imaging can providesituation of whole or regional cerebral blood flowperfusion (CBF or rCBF) to neurologists, help to findabnormality of cerebral blood flow before cere-brovascular and neurological diseases induce patho-logical changes in configuration or structure of brain.They offer important information for …     

Labeling of ursodeoxycholic acid with technetium-99m for hepatobiliary imaging

An adopted method for the preparation of high radiochemical purity ^99mTc-ursodeoxycholic acid (UDCA) was conducted with a high radiochemical yield up to 97.5 %. The reaction proceeds well using 2 mg UDCA, 50 μg tin chloride in solution of pH 8 at room temperature for 30 min. The radiochemical yield was up to 97.5 % as pure as ^99mTc-UDCA. Different chromatographic techniques (paper chromatography and electrophoresis) were used to evaluate the radiochemical yield and purity of the labeled product. Biodistribution studies were carried out in Albino Swiss mice at different time intervals after administration of ^99mTc-UDCA. The uptake of ^99mTc-UDCA in the liver gave the chance to diagnose it. The results indicate that the labeled compound cleared from the systematic circulation within 2 h after administration and majority of organs showed significant decrease in uptake of ^99mTc-UDCA. Finally, the liver uptake was high and the results indicate the possibility of using ^99mTc-UDCA for hepatobiliary imaging.     

Determination of complex forming conditions of 8-hydroxyquinoline with technetium-99m

Complex forming conditions of 8-hydroxyquinoline with^99mTc have been specified.^99mTcO₄ ^– has been reduced by SnCl₂ to a lower oxidation level. Labeling yields have been determined by ITLC (Instant Thin Layer Chromatography). Various parameters, such as pH, temperature, reaction time, ligand to SnCl₂ ratio, which can affect the labeling yields, have been determined. Optimum conditions are 4–7 for pH; 15–20°C (room) for temperature; 1.55 for ligand to SnCl₂ ratio and 5 min for reaction time.     

Synthesis and properties of neutral gadolinium and technetium-99m-labeled complexes

Diethylenetriaminepentaacetic di(L-dopa ethyl ester) ligand (DTPA-2LDEE) was synthesized by reaction between diethylenetriaminepentaacetic dianhydride (DTPAA) and L-dopa ethyl ester (LDEE). This ligand reacted with gadolinium chloride and sodium pertechnetate to make the corresponding neutral gadolinium complex Gd-DTPA-2LDEE and technetium-99m-labeled complex ^99mTc-DTPA-2LDEE, respectively. The ligand and complexes were characterized and their properties in vitro and in vivo were also evaluated. Gd-DTPA-2LDEE possessed higher relaxation effectiveness and lower cytotoxicity to human hepatoma HepG-2 cells than Gd-DTPA. ^99mTc-DTPA-2LDEE had enhanced single-photon emission computed tomography (SPECT) signal enhancements of the kidneys in rats and provided longer duration time than that of ^99mTc-DTPA. Therefore, ^99mTc-DTPA-2LDEE can be selectively excreted by the kidneys and used as a potential radioactive probe in SPECT.     

Radiolabeling of low molecular weight d-galactose-based glycodendrimer with technetium-99m and biodistribution studies

Glycodendrimers are neoglycoconjugates that can be considered as bioisosters of glycoproteins, since they can mimic the multivalent interactions of lectin-carbohydrate. The ability of glycodendrimers to present multivalent interactions with lectins as compared to a monovalent ligand is referred to as “cluster effect”. It is expected that, because of the cluster effect, glycodendrimers would result in a better association with lectins than mono-carbohydrate anchored systems. Radioisotopes are useful to evaluate biodistribution of molecules. This study is important to obtain information about molecule–receptor interactions. Indeed, such study can provide an exquisite tool to evaluate the affinity of certain molecules to specific areas in the body, leading to the development of new radiopharmaceuticals and/or drug delivery systems. Herein, we describe a d-galactose coated low molecular weight PAMAM G0 dendrimer that was successfully radiolabeled with technetium-99m. Biodistribution studies and scintigraphic images were performed in healthy mice. It was observed high liver uptake which was significantly reduced in blocking studies, indicating hepatic specificity. Therefore, low molecular weight glycodendrimer can be considered as useful platform for selective targeting of drugs to the liver and to assess hepatic function.     

Kit development for labelling erythrocytes or leukocytes with technetium-99m in vitro

Positron lifetime spectroscopy has been applied to estimate the free-volume hole size distribution in glassy polycarbonate (PC) and polystyrene (PS) as well as in plastically deformed and undeformed, semi-crystalline polyethylene (HDPE). The hole radius density distribution is determined from the ortho-positronium lifetime distribution which is obtained via a Laplace-inversion of the positron lifetime spectrum. The hole volume density distribution and the number density distribution of holes is estimated from the hole radius density distribution. In PC and in PS all of the distributions may be well approximated by a single Gaussian. The hole radius and the hole number density distributions have centres <r> and <v _n > at 0.29 nm and 0.1 nm³ in PC, and at 0.28 nm and 0.09 nm³ in PS. The FWHM of the corresponding distributions are 0.042 nm and 0.040 nm³ (PC), and 0.039 nm and 0.34 nm³ (PS), respectively. Both, the shape and the width of the distributions correlate well with the free volume theory of BUECHE. In PE the lifetime spectra consist of four components. The o-Ps lifetime distribution is bimodal and may be attributed to o-Ps annihilation in the crystalline and in the amorphous phase of the polymer. The corresponding hole size distributions show definite changes of their position and width following plastic deformation which we attribute to homogeneous crystal lattice dilatation and/or a local disorder in the crystals and to an increase in the eccentricity of holes in the amorphous phase.     

The structure of lanthanide complexes with five membered sulfones and the specific benzene solvation

By means of a computer program based on the pseudo-contact equation, the structures of lanthanide complexes with five-membered sulfones have been established. The compounds are 1:1 bidentate complexes with the axis of complexation nearly parallel to the bisecting line of the O-S-O angle, and with the lanthanide position being at an average distance of 2.4 A from both oxygen atoms. The Ledal model, which assumes the specific benzene solvation, has been proposed as an adequate model for molecules with planar ring structure, and the distance between the benzene and solute along the preferential axis of complexation has been established as ~ 3.0 Å. The most probable conformation of the ring was taken into account because the accuracy of location of the lanthanide or benzene molecule in these complexes depends mainly on the correct model of the molecule assumed. Detailed analysis of the Eu(fod),-induced shifts in the PMR spectrum of NTBN sulfone confirmed the advanced structure of the complexes of five-membered ring sulfones with the lanthanide shift reagents.     

Technetium-99m complexes with steroid-2-aminooxyethyliminodiacetic acid conjugates

Conjugates of 2-aminooxyethyliminodiacetic acid with estrone, testosterone, epiandrosterone, 17-alpha-hydroxy-progesterone and progesterone were synthesized and their complexes with Tc-99m were successfully prepared in good yields, which indicated the agent to be promising for metal-labeling of biomolecules and related substances containing one or more carbonyl groups. The biodistribution and scintigraphic studies in mice bearing Ehrlich tumor and mammary tumor showed that the radioactivity accumulated considerably in the tumor tissues, but the tumor images were somewhat obscured.     

Electronic structure and bonding studies on triple-decker sandwich complexes with a P6 middle ring

DFT and hybrid HF-DFT studies of structure and bonding of CpMP6MCp triple-decker sandwich complexes, ranging from 18-28 valence electrons (VE) with M=Sc, Y, Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, and W, show that the middle P6 ring complexes adopt symmetric planar (28 valence electron count [VEC]), asymmetric planar (26 VEC), and puckered (24 VEC) geometries. According to the mno Rule, 50 skeletal electrons are needed for these triple-decker cluster frameworks. For 28 VEC, this corresponds to 10 electrons more than the 50 electrons of the mno Rule if all VE of the metal are included. These additional electrons control the distortion of a P6 middle ring and other finer structural details. Completely filled 2a* and 2b* orbitals in 28 VE complexes lead to a planar symmetrical P6 middle ring, while the occupancy in either 2a* or 2b* alone explains the in-plane distortions (asymmetric) in 26 VE complexes. In comparison with 28 VE complexes, the puckering of P6 middle ring in 24 VE complexes is due to the greater stabilization of 5a and the extra stabilization of the +4 oxidation state of Ti. The quintet state of 22 VE complexes is planar as 2a* and 2b* are half filled. Similar geometrical and bonding patterns of CpScP6ScCp and C2P3H2ScC3P3H3ScC2P3H2 support the carbon-phosphorus analogy further. The 18 VE systems, CpScC3B3H6ScCp+ and CpScP3B3H3ScCp+, have the 50 skeletal electrons as stipulated by the mno Rule. Corresponding anions have 52 skeletal electrons (20 VE); the middle rings here are distorted in the plane.     

Synthesis and structure of nickel and copper chelate complexes with coumarin azo ligand

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Synthesis and preliminary biological evaluation of a technetium-99m labeled thymidine analog

The synthesis and labeling of ^99mTc-N³-（N’-[2-sulfanyl-ethylamino）acetyl]-2-aminoethyl-sulfanyl-1-hexanamide}thymidine (^99mTc-NHT) were studied.In the presence of sodium glucoheptonate（GH） and ethylene diamine tetraacetic acid（EDTA）,^99mTc-NHT was obtained by using bisaminoethanethiol（N₂S₂） as a bifunctional coupling agent.The radiochemical purity of the ^99mTc-NHT was over 95%.Biodistribution of ^99mTc-NHT was performed in hepatoma HepA tumor-bearing mice.At 2 h p.i.,the ratios of tumor-to-muscle,tumor-to-bone and tumor-to-blood were 4.41±0.32,2.45±0.24 and 1.51±0.18,respectively.     

Direct labeling of doxorubicin with technetium-99m: its optimization, characterization and quality control

Doxorubicin (DOX) is an anthracycline antineoplastic and one of the most potent and widely used drugs in clinical oncology. It is used in the treatment of a wide variety of cancers. The aim of this study was the direct labeling of DOX with ^99mTc; its optimization, characterization and quality control of the radiolabeled DOX. Labeling efficiency was determined by paper chromatography. More than 92% labeling was obtained at pH 6?C7, 10?C12???g stannous chloride and 200???g of DOX. The stability of ^99mTc?CDOX was studied up to 5?h. All the experiments were performed at room temperature (25±?2?°C). The characterization of the labeling compound was performed by HPLC and electrophoresis. Electrophoresis indicates that labeled DOX has no charge and HPLC shows single specie of labeled compound.     

Platelet-12 lipoxygenase targeting via a newly synthesized curcumin derivative radiolabeled with technetium-99m

Background

One of the most popular techniques for cancer detection is the nuclear medicine technique. The present research focuses on Platelet-12-lipoxygenase (P-12-LOX) as a promising target for treating and radio-imaging tumor tissues. Curcumin was reported to inhibit this enzyme via binding to its active site.

Results

A novel curcumin derivative was successfully synthesized and characterized with yield of 74%. It was radiolabeled with the diagnostic radioisotope technetium-99m with 84% radiochemical yield and in vitro stability up to 6 h. The biodistribution studies in tumor bearing mice confirmed the high affinity predicted by the docking results with a free binding energy value of (ΔG ?50.10 kcal/mol) and affinity (13.64 pki) showing high accumulation in solid tumor with target/non-target ratio >6.

Conclusion

The newly synthesized curcumin derivative, as a result of a computational study on platelet-12 lipoxygenase, showed its excellent free binding energy (?G ?50.10 kcal/mol) and high affinity (13.64 pKi). It could be an excellent radio-imaging agent that targeting tumor cells via targeting of P-12-LOX.

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Graphical abstract This novel curcumin derivative was successfully synthesized and radiolabeled with technetium-99m and biologically evaluated in tumor bearing mice that showed high accumulation in solid tumor with target/non-target ratio >6 confirming the affinity predicted by the docking results. Predicted binding mode of a new curcumin derivative in complex with 12-LOX active site. b Curcumin itself in the 12-LOX active site biological distribution of ^99mTc-curcumin derivative complex in solid tumor bearing Albino mice

     

Photoelectron spectra and electronic structure of nitrogen-containing chelate boron complexes

A brief review of the results of studying some classes of nitrogen-containing chelate boron complexes by ultraviolet photoelectron spectroscopy and density functional theory is reported. The quantum chemical modeling of the substitution effects of a complexing agent, heteroatoms, and functional groups in α, β, and γ positions of the chelate ring allowed us to establish the features of the electronic structure of the studied complexes. It is found that the substitution of heteroatoms in the chelate ring has no substantial influence on the structure of the highest occupied molecular orbital (HOMO). In imidoylamidinate complexes, as opposed to formazanates and β-diketonates, there is no noticeable mixing of π orbitals of the chelate and benzene rings. In condensed nitrogen heterocycles the HOMO is stabilized by 0.2-0.3 eV and π orbitals of the benzene ring are stabilized by 0.8-1.2 eV. The HOMO of substituted aza-boron-dipyridomethene correlates with anthracene and acridine π₇ orbitals, which causes the fine structure of the first band. It is shown that in an energy range below 11 eV the calculated results reproduce well the energy gaps between the ionization states of the complexes.     

Chemical and biological properties of verapamil labeled with technetium-99m: A potential myocardial imaging agents

On the base of property to enter into myocardial cells as a calcium channel blocker, verapamil was labeled with technetium-99m in order to investigate the possibility to obtain new radiopharmaceutical for myocardial imaging. The conditions of labeling verapamil with technetium-99m for different ammounts of stannous(II) ion, mannitol, cystein and pH range 2.5–3.5 were examined. Investigation of radiochemical purity (>95%) and biodistribution of ^99mTc-verapamil in rats showed that it was stable during 2 hours after labeling. Accumulation of ^99mTc-verapamil in heart was 1.2% and in liver 9.4%, 5 minutes after injection. Biodistribution of ^99mTc-verapamil in rats in conditions of stress, pharmacologically caused by dipiridamol, showed that the elimination of ^99mTc-verapamil from the heart was slower related to the control group. In the group of rats previously treated with isoproterenol uptake of ^99mTc-verapamil in heart was lower related to the control group (0.7% versus 1.0%) 5 minutes after injection. Lipophilicity of ^99mTc-verapamil was examined by determination of partition coefficient (log P = 0.62) and protein binding (79%). Imaging studies on dogs provided relatively good myocardial images with partially overlap of activity in the lung and liver.