Vascular responses to endovascular irradiation of 188Re in the rabbit model after angioplasty

The effects on vascular restenosis of intravascular radiation delivery from ¹⁸⁸Rhenium (Re)-perrhenate liquid-filled balloon through beta-particle radiation are controversial. To determine the effect of beta-radiation on vascular injury in hypercholesterolemic rabbits, thirty rabbits fed with a high cholesterol diet were enrolled into this study. All the rabbits underwent percutaneous transluminal balloon overstretch over left iliac artery. After balloon overstretch, the catheter was withdrawn and immediately followed by irradiation using low dose ¹⁸⁸Re solution (10 Gray) in the vascular wall 0.5 mm distal to intimal surface. After 2 and 6 weeks, arteries were harvested for histological and immunological analysis. This rabbit study suggest that endovascular ¹⁸⁸Re low dose irradiation at the non-injury segment of iliac artery may enhance intima hyperplasia and smooth muscle cell proliferation.     

Production of carrier-free 188Re in the past ten years in Taiwan

Twenty clinical scale alumina-based ¹⁸⁸W/¹⁸⁸Re generators and carrier-free ¹⁸⁸Re has been produced at the Institute of Nuclear Energy Research (INER-Taiwan) for over ten years. 2845.6 GBq (76.9 Ci) of ¹⁸⁸Re-perrhenate solution has been eluted from generators during the past ten years. We have used the harvesting ¹⁸⁸Re solution for labeling radiopharmaceuticals, such as ¹⁸⁸Re-HEDP, ¹⁸⁸Re-MDP, ¹⁸⁸Re-microsphere, ¹⁸⁸Re-lipiodol, and ¹⁸⁸Re-sulfur colloid, etc. The average eluting yield of ¹⁸⁸Re is 78.6±5.8% that was investigated at 1115 harvesting times from 20 generators. Each generator can be used more than six months but the Millipore needs to be changed every two months for smooth harvesting and high yield of ¹⁸⁸Re solution.     

Local delivery of rhenium-188 colloid into hepatic tumor sites in rats using thermo-sensitive chitosan hydrogel: effects of gelling time of chitosan as delivery system

A previously developed internal radiation therapy mode adopting a thermo-sensitive, chitosan-based hydrogel intended for local delivery of ¹⁸⁸Re–Tin colloid drug was extended to test for its applicability to the treatment of hepatoma in rats. The effects of two formulations of hydrogel with different gel times and two methods of delivering the hydrogel containing ¹⁸⁸Re–Tin colloid into tumors on the accumulated dose and duration of radioactivity within tumor were first studied by in vitro release, planar scintigraphy, and bio-distribution evaluations. Results from this initial study suggest that a treatment mode using the intratumoral delivery method and a 4 min gel time hydrogel to deliver the ¹⁸⁸Re–Tin colloid into the tumor is more effective for treating hepatoma in rats. The treatment mode was then further verified through efficacy evaluations based on hepatic tumor growth in hepatoma-bearing rats. In conclusion, the application of chitosan/β-glycero-phosphate (C/GP) hydrogel for the local delivery of ¹⁸⁸Re–Tin colloid to treat hepatoma in rats is feasible. The effective and efficient treatment mode consists of the intratumoral injection of ¹⁸⁸Re–Tin colloid premixed with 4 min gel time C/GP hydrogel.     

A new technique for labeling of Lipiodol with 188Re in the treatment of hepatic tumor

A new method for the synthesis of ¹⁸⁸Re-Lipiodol without using a chelating agent and to evaluate the stability and biodistribution of the new agent in rats with hepatic tumors was attempted. Eighteen male Sprague -Dawley rats with liver tumors were sacrificed at 1, 24, and 48 hours (six rats at each time) after injection of approximately 7.4 MBq (0.2 mCi) of ¹⁸⁸Re Lipiodol via the hepatic artery. Samples of tumor, liver and other organs were collected and tissue concentration (%ID/g) of the markers were calculated. Our data showed a high level of radioactivity in the hepatic tumors at every time of the study. The ratios of tumor to normal liver tissue concentration (T/N ratio) were 7.62 at 1 hour, 8.03 at 24 hours, and 7.70 at 48 hours. Except for the liver, kidneys and lungs, concentrations in other organs were low. The new method for labeling Lipiodol with ¹⁸⁸Re is simple and has potential for the treatment of hepatic tumors This revised version was published online in July 2006 with corrections to the Cover Date.     

Synthesis, in vitro and in vivo behavior of 188Re(I)-tricarbonyl complexes for the future functionalization of biomolecules

Radiolabeling of biologically active molecules with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ unit has been of primary interest in recent years. Therefore, we herein report ligands L¹−L⁴ (L¹=histidine, L²=nitrilotriacetic acid, L³=2-picolylamine-N,N-diacetic acid, L⁴=bis(2-pyridymethy)amine) that have been evaluated by radiochemical reactions with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺. These reactions yielded the radioactive complexes of fac-[¹⁸⁸Re(CO)₃L] (L = L¹−L⁴, ¹⁸⁸Re tricarbonyl complexes 1–4), which were identified by HPLC. Complexes 1–4, with log P _o/w values ranging from −2.23 to 2.18, were obtained with yields of ≥95% using ligand concentrations within 10⁻⁶–10⁻⁴M range. Thus, specific activities of 220 GBq/μmol could be achieved. Challenge studies with cysteine and histidine revealed high stability for all of these radioactive complexes, and biodistribution studies in mice indicated a fast rate of blood clearance and high rate of total radioactivity excretion occurring primarily through the renal-urinary pathway. In summary, the ligands L¹–L⁴ are potent chelators for the future functionalization of biomolecules labeling with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺.     

Investigation of the phase behavior of an embedded charge protein model through molecular simulation

The phase behavior of an embedded-charge model for lysozyme developed by Carlsson and co-workers (J. Phys. Chem. B 2001, 105, 9040) is investigated using grand canonical transition matrix Monte Carlo simulation. Within this model, protein-protein interactions are approximated through a combination of hard-sphere repulsion, isotropic hydrophobic attraction, and screened electrostatic interactions through a series of embedded point charges located at the positions of charged amino acid groups within lysozyme. Liquid-liquid phase diagrams are constructed for a wide range of solution conditions and compared with experimental data. Our results indicate that the model is generally capable of describing qualitative trends in the evolution of protein phase behavior with variation of pH and ionic strength. From a quantitative perspective, model estimates for both the change in critical temperature with variation of the solution conditions and the critical concentration do not agree with experimental results. We find the width of model coexistence curves to be independent of solution conditions and narrow relative to experimentally obtained phase envelopes. Connections between the value of the second virial coefficient evaluated at the critical temperature and the location of the liquid-liquid phase envelope are also examined.     

Preparation and characterization of a novel magnetized nanosphere as a carrier system for drug delivery using Plantago ovata Forssk. hydrogel combined with mefenamic acid as the drug model

The aim of the present study was to magnetize Plantago ovata Forssk. hydrogel and produce a nanosphere system to carrier mefenamic acid as the drug model. For this propose, P. ovata seeds hydrogel (POSH) was extracted and magnetized by Fe₃O₄ being functionalized using tetraethyl orthosilicate and trimethoxyvinysilane. Thereafter, mefenamic acid (MFA) was loaded on the carrier system. The final product, as the magnetic drug loaded nanosphere (Fe/POSH/MFA), was fully characterized through different techniques involving X-ray diffraction (XRD), scanning electron microscopy (SEM), vibrating-sample magnetometer (VSM), thermal gravimetric analysis (TGA), dynamic light scattering (DLS), and FT-IR spectroscopy. The results confirmed the successful production of the drug loaded nanosphere system with particles magnetization of 25 emu/g over a range size of 40–50 nm. However, the size distribution less than 100 nm was measured through DLS analysis. The hydrogel showed a pH sensitivity swelling behavior representing the best efficacy at pH 7.4. The efficiency of the drug encapsulation was found to be 64.35%. The drug releasing was studied using a dialysis bag at pH = 7.4. The highest in vitro drug releasing was found to be 57.3 ± 0.6% after 72 h, as well. The findings of the current report account for the potential use of P. ovata hydrogel as an effective delivery system for encapsulation of water insoluble basic drugs, e.g., MFA in a magnetized carrier system.     

Parthenolide-induced apoptosis of hepatic stellate cells and anti-fibrotic effects in an in vivo rat model

Parthenolide (PT), a sesquiterpene lactone derived from the plant feverfew, has pro-apoptotic activity in a number of cancer cell types. We assessed whether PT induces the apoptosis of hepatic stellate cells (HCSs) and examined its effects on hepatic fibrosis in an in vivo model. The effects of PT on rat HSCs were investigated in relation to cell growth inhibition, apoptosis, NF-κB binding activity, intracellular reactive oxygen species (ROS) generation, and glutathione (GSH) levels. In addition, the anti-fibrotic effects of PT were investigated in a thioacetamide-treated rat model. PT induced growth inhibition and apoptosis in HSCs, as evidenced by cell growth inhibition and apoptosis assays. PT increased the expression of Bax proteins during apoptosis, but decreased the expression of Bcl-2 and Bcl-X(L) proteins. PT also induced a reduction in mitochondrial membrane potential, poly(ADP-ribose) polymerase cleavage, and caspase-3 activation. PT inhibited TNF-α-stimulated NF-κB binding activity in HSCs. The pro-apoptotic activity of PT in HSCs was associated with increased intracellular oxidative stress as evidenced by increased intracellular ROS levels and depleted intracellular GSH levels. Furthermore, PT ameliorated hepatic fibrosis significantly in a thioacetamide- treated rat model. In conclusion, PT exhibited pro-apoptotic effects in rat HSCs and ameliorated hepatic fibrosis in a thioacetamide-induced rat model.     

Determination of antiviral nucleoside analogues AM365 and AM188 in perfusate and bile of the isolated perfused rat liver using HPLC

Development, validation and application of an HPLC assay for new antiviral nucleoside analogues AM365 and AM188 in isolated perfused rat liver perfusate and bile were performed. An analytical column (Phenosphere-NEXT, 250 x 4.6 mm, C(18), 4 microm, Phenomenex) was used in tandem with a guard column (4 x 3 mm, C(18), Phenomenex) and operated at 25 degrees C. The mobile phase [methanol:10 mmol/L sodium orthophosphate buffer (pH 7.0), 15:85, v/v] was pumped at 1 mL/min. The signal from a diode array detector was collected from 190 to 300 nm. The chromatogram was processed at 220 and 252 nm for AM365 and AM188, respectively. The HPLC method was validated by six intraday and seven interday runs. Standard curves were linear in the range 0.125-8.00 microg/mL for AM365 and AM188, and the lower limit of quantification for AM365 and AM188 was 0.125 microg/mL. Mean interday precision and accuracy of IPL perfusate quality control samples were within 8.8%, and mean intraday precision and accuracy were within 13.1%. The assay has been successfully used in the study of metabolism and disposition of AM365 in the isolated perfused rat liver.     

Development and use of an economic evaluation model to assess establishment of local centralized rural biogas plants in Greece

An economic evaluation model was developed in the Laboratory of Agricultural Structures (LAS) of the Agricultural University of Athens—the Modified Basic Economic Evaluation Model (MBEEM). This model is an improved version of the original Basic Economic Evaluation Model, available in LAS, and it is used to assess the cost-effectiveness of biogas production systems. Because of the parameters involved, a computer model was developed to facilitate the application of the MBEEM. The model was used in this work to determine the cost-effective size of a local centralized biogas production system fed with pig wastes.     

A Re(CO)5 fragment bonded to a polyhedral oligomeric hydroxysilsesquioxane as a model which gives further evidence to the existence of an unexpected Re(CO)5 surface species

Reaction of Re(CO)5O3SCF3 with (c-C6H11)7Si8O12O-Li+ at 273 K under a CO atmosphere affords the [Re(CO)5OR] (R = (c-C6H11)7Si8O12) derivative (1). 1 is the first example of a rhenium pentacarbonyl bearing an OR ligand (R = alkyl, aryl, or silyl) stable enough to be characterized, and it represents also the first molecular model of the surface [Re(CO)5OSi] species formed by reductive carbonylation of silica-supported [Re(CO)3OH]4. At room temperature, 1 loses one carbonyl ligand and dimerizes to afford {Re(CO)4[(mu-O)O12Si8(c-C6H11)7]}2 (2), which has been characterized by X-ray diffraction and is the first reported example of a rhenium tetracarbonyl mu-oxo-bridged dimer of the type [Re(CO)4(mu-OR)]2.     

Comparison of the efficacy of 177Lu-EDTMP, 177Lu-DOTMP and 188Re-HEDP towards bone osteosarcoma: an in vitro study

Among the radiopharmaceuticals harnessed for palliation of bone pain in osseous metastases patients, ¹⁷⁷Lu labeled phosphonates such as EDTMP (Ethylene diamine tetramethylene phosphonic acid) as well as DOTMP (1,4,7,10-tetraaza-cyclo-dodecane-1,4,7,10 tetraethylene phosphonic acid) and ¹⁸⁸Re-labeled HEDP (1,1-hydroxyethylene diphosphonic acid) seem to be the most favorable for treatment of small and medium/large size bone lesions, respectively. A comparative assessment of ¹⁷⁷Lu-EDTMP, ¹⁷⁷Lu-DOTMP and ¹⁸⁸Re-HEDP in osteosarcoma tumor cell line was carried out to evaluate their relative efficacy. It was found that ¹⁸⁸Re-HEDP is more potent in induction of cell toxicity and apoptosis compared to the ¹⁷⁷Lu-EDTMP and ¹⁷⁷Lu-DOTMP, thus ¹⁸⁸Re-HEDP might have great clinical significance.

     

Investigation of EPR parameters and the local structure of the rhombic Cu2+ center in zinc fluoride

Based on a cluster approach, the local structure of the rhombic Cu²⁺ center in a ZnF₂ crystal is investigated by using the high-order perturbation formulas of electron paramagnetic resonance (EPR) parameters g factors g _i (i = x, y, z) and hyperfine structure constants A _i in rhombically compressed octahedral symmetry. According to the studies, the local axial distortion angle Δα′(≈ 2.9°) in the impurity center is found to be by ～2.5° larger than the host value, which is characterized as a contraction and stretching of the parallel and perpendicular bond lengths by about 0.116 Å and 0.058 Å respectively. This results in a more compressed ligand octahedron because of the Jahn-Teller effect via the interaction of the vibrations of impurity-ligand bonds in the Cu²⁺ center. The reasonableness of the results is also discussed.     

Efficient exosome extraction through the conjugation of superparamagnetic iron oxide nanoparticles for the targeted delivery in rat brain

Exosomes possess endogenous attributes and distinct biological functions, and thereby, their uses as drug nanocarriers have attracted increasing attention for biomedical practices. However, to achieve targeted therapeutic purposes, complicated extractions, as well as modifications of exosomes, are involved. Here, based on the use of superparamagnetic iron oxide nanoparticles conjugated exosome (Ex-SPIONs), a facile exosome extraction through magnetism was established. The produced Ex-SPIONs exhibited a uniform size distribution and desirable biocompatibility. Moreover, taking advantage of the magnetic properties of SPIONs, the targeted delivery of Ex-SPIONs was demonstrated in the rat brain. Therefore, the constructed SPIONs functionalized exosome shows promising therapeutic potentials, including the treatment of brain diseases.     

Investigation of intramolecular proton migration in a series of model, metal-cationized tripeptides using in situ generation of an isotope label

In this study we used an isotope label, generated in situ, to investigate intramolecular proton migration or scrambling during formation of [b(2)+17+Li](+) products by collision-induced dissociation (CID) of Li(+)-cationized tripeptides. To generate the isotope label, we used a McLafferty-type rearrangement of N-terminally acetylated, C-terminal peptide tert-butyl esters in which all amide positions were exchanged with deuterium. Using a set of small, model peptides, we show that intramolecular proton scrambling occurs during CID, particularly amongst adjacent sites along a peptide backbone, on the time scales employed for low-energy collisional activation in an ion-trap mass spectrometer.     

Measurement of the local temperature in an ion track using low-dimensional quantum confinement structure

We measured the local temperature in an ion track utilizing fast exciton recombination in (C₃H₇NH₃)₂PbBr₄. We obtained the local temperatures of 1000–1500 K for 1.0 MeV H⁺, 2.0 MeV H⁺ and He⁺, and the local temperature was found to be an increasing function of the linear energy transfer. Furthermore, the measured local temperature increased with increasing ion dose, which is attributed to the diffusion of the phonons in an ion track.