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A comparative study of the safety and efficacy of dysprosium-165 hydroxide macro-aggregate and yttrium-90 silicate colloid in radiation synovectomy--a multicentre double blind clinical trial. Australian Dysprosium Trial Group.

The aim of our study was to compare the safety and efficacy of a new preparation, Dysprosium-165 Hydroxide Macroaggregate (165Dy) with Yttrium-90 Silicate (90Y) for radiation synovectomy of the knee in patients with RA and OA. A multicentre double blind clinical trial with subjects randomized to receive 165Dy or 90Y was undertaken in Sydney, Melbourne and Perth. Seventy knees of 59 patients were studied, using as clinical end point measurements, pain in the knee on walking, pain in the knee at rest and stiffness in the knee after rest. Cytogenetic damage, knee retention and extra-articular spread of the radionuclide to regional lymph nodes, liver, urine and blood were evaluated. There was no significant difference in clinical response in the two treatment groups for either RA or OA. Chromosomal changes occurred with equal frequency and the knee retention and extra-articular leakage of radiocolloids to regional lymph nodes and liver were comparable in the two groups. For radiation synovectomy of the knee, 165Dy is at least as safe and as effective as 90Y and has the advantage of a short half-life (2.334 h) and hence requires a shorter period of post-injection immobilization and hospitalization.

Aged↗

Dysprosium as a nonabsorbable fecal marker in studies of zinc homeostasis.

BACKGROUND: Dysprosium is a nonabsorbable rare earth element that has had successful application as a marker for fecal excretion of unabsorbed zinc. OBJECTIVE: Our goals were 1) to evaluate the efficacy of administering dysprosium with all meals over several days as a method of determining the completeness of fecal collections, 2) to determine the similarity of gastrointestinal transit kinetics and excretion patterns of dysprosium and zinc tracer administered simultaneously over several days, and 3) to evaluate alternative methods of using the data for fecal excretion of orally administered zinc tracer and dysprosium to measure the fractional absorption of zinc. DESIGN: 70Zn and dysprosium were administered orally with all meals for 5 consecutive days to 7 healthy, free-living adults consuming a constant diet based on habitual intake. Additional tracers, 67Zn and 68Zn, were administered intravenously. Urine and fecal samples were collected during tracer administration and for 8 d after the last dose. Isotope ratios were measured in urine and feces, and total zinc and dysprosium were measured in fecal samples. RESULTS: The mean recovery of dysprosium was 101.3 +/- 2.4%. The zinc oral tracer and dysprosium had similar fecal excretory patterns; the correlation coefficient for 70Zn and dysprosium in fecal samples exceeded 0.99 (P < 0.0001) for each subject. Fractional zinc absorption measurements using various dysprosium methods correlated well (r > 0.95) with those from the fecal monitoring and dual-isotope-tracer ratio methods. CONCLUSION: Administration of dysprosium is a useful means of determining the completeness of fecal collections and of measuring zinc absorption.

Administration, Oral↗

Effect of dysprosium on the spin-lattice relaxation time of cytochrome c and cytochrome a.

The progressive power saturation of the electron paramagnetic resonance of horse heart cytochrome c and solubilized bovine heart cytochrome oxidase has been monitored at low temperature in the presence of the relaxing agent, dysprosium. The saturation of the EPR signal of cytochrome c is relieved even at 6 K. With increasing temperature the effect is enhanced as the relaxation time of the dysprosium becomes shorter; however, the intrinsic spin-lattice relaxation time, T1, for cytochrome c decreases even more rapidly with increasing temperature. T1 for cytochrome c can be described by an intrinsic component, a component which is proportional to the concentration of dysprosium and a third component due to local binding which is independent of dysprosium concentration. The cytochrome a component of cytochrome oxidase is also affected by dysprosium. In the presence of cytochrome oxidase, T1 for cytochrome c is almost unaffected by dysprosium, indicating that access to the cytochrome c heme is blocked by the binding of c to oxidase. Based on the concentration-dependent effect of dysprosium on the lifetime of cytochrome c, it is possible to make distance estimates from the EPR active center to Dy3+. Dysprosium is therefore useful for determining the spatial relationships among paramagnetic enzyme components in a quantitative way.

Animals↗

Dysprosium-bearing red cells as potential transverse relaxation agents for MRI.

The cytosol of intact human red blood cells was loaded with 28.1 +/- 3.4 mM of dysprosium DTPA-BMA using a hypoosmotic technique. When loaded cells were diluted with saline and control cells to give an average dysprosium concentration of 3.3 +/- 0.5 mM, the transverse relaxation rate constants R(*)(2) and R(2) increased. R(*)(2) increased from 7.5 +/- 0.9 sec(-1) to 356 +/- 50 sec(-1), and R(2) increased from 7.4 +/- 0.7 sec(-1) to 148 +/- 40 sec(-1). After lysing, R(*)(2) was 6.0 +/- 0.6 sec(-1) in the control and 13.4 +/- 1.5 sec(-1) in the mixture; R(2) was 6.4 +/- 1.1 sec(-1) and 9.8 +/- 2.4 sec(-1), respectively. Thus, the relaxivity effects were enhanced by sequestration of the dysprosium within intact red cells, and this effect was lost after lysis. At a circulating whole-blood concentration of 0.81 +/- 0.15 mM in rats, the liver signal intensity dropped 29.9% +/- 3.7% and kidney signal intensity dropped 19.4% +/- 8.7%. Dysprosium-loaded cells might be useful in the study of perfusion and tissue blood volume.

Animals↗

Monitoring of the effects of dysprosium shift reagents on cell suspensions.

The effects of two widely used paramagnetic shift reagents for cationic NMR, dysprosium tripolyphosphate [Dy(PPP)2(7-)] and dysprosium triethylenetetramine hexaacetate [Dy(TTHA)3-], on the cell structure of dog and human erythrocytes, dog kidney cortical tubules and rat hepatocytes were investigated. The effect of shift reagents on cell integrity was monitored by measuring the hematocrit values for erythrocytes, by measuring the lactate dehydrogenase (LDH) release and by electron microscopy for cortical tubules and hepatocytes. The quantitation of the dyprosium penetration inside cells was accomplished by atomic absorption, atomic emission and neutron activation. More severe effects were observed with Dy(PPP)2(7-) than with Dy(TTHA)3-, and were dependent on the divalent cation concentration and on the shift reagent concentration. Very serious cell damage was observed after 60 min incubation in the presence of 10 mumol Dy(PPP)2(7-)/mL suspension at low or high divalent cation concentration. The situation was improved at 5 mumol Dy(PPP)2(7-)/mL suspension especially at high divalent cation concentration (2.5 mM). Incubation with Dy3+, PPP5- or Dy(TTHA)3- caused little or no structural effects but dysprosium was found to penetrate slowly inside tubules with Dy(TTHA)3-. Both Dy3+ and Dy(PPP)2(7-) penetrated rapidly inside cells. Dysprosium was found to bind to the isolated cytosol but not to isolated membranes, eliminating the possibility of extracellular membrane binding.

Animals↗

Dysprosium (165Dy) hydroxide macroaggregates for radiation synovectomy--animal studies.

This paper reports the development of a new chemical formulation, Dy-HMA, to utilise the advantages of dysprosium 165 in radiation synovectomy of certain forms of arthritis. Dy-HMA is a sterile suspension of dysprosium hydroxide macroaggregates (approximately 6 mg Dy/ml) in saline with the majority of particles in the 3-5 microns range. The absence of ferric hydroxide and a higher concentration of dysprosium in the formulation offer advantages over dysprosium ferric hydroxide macroaggregates, Dy-165-FHMA. Biodistribution studies in rats and rabbits with Dy-HMA show less leakage than with Dy-FHMA and considerably less leakage than with yttrium silicate colloid. Rabbits treated with intra-articular injections of Dy-HMA equivalent to 10-30 times the typical clinical dose showed no signs of any toxic effects.

Animals↗

On-line complexation/cloud point preconcentration for the sensitive determination of dysprosium in urine by flow injection inductively coupled plasma-optical emission spectrometry.

An on-line dysprosium preconcentration and determination system based on the hyphenation of cloud point extraction (CPE) to flow injection analysis (FIA) associated with ICP-OES was studied. For the preconcentration of dysprosium, a Dy(III)-2-(5-bromo-2-pyridylazo)-5-diethylaminophenol complex was formed on-line at pH 9.22 in the presence of nonionic micelles of PONPE-7.5. The micellar system containing the complex was thermostated at 30 degrees C in order to promote phase separation, and the surfactant-rich phase was retained in a microcolumn packed with cotton at pH 9.2. The surfactant-rich phase was eluted with 4 mol L(-1) nitric acid at a flow rate of 1.5 mL min(-1), directly in the nebulizer of the plasma. An enhancement factor of 50 was obtained for the preconcentration of 50 mL of sample solution. The detection limit value for the preconcentration of 50 mL of aqueous solution of Dy was 0.03 microg L(-1). The precision for 10 replicate determinations at the 2.0 microg L(-1)Dy level was 2.2% relative standard deviation (RSD), calculated from the peak heights obtained. The calibration graph using the preconcentration system for dysprosium was linear with a correlation coefficient of 0.9994 at levels near the detection limits up to at least 100 microg L(-1). The method was successfully applied to the determination of dysprosium in urine.

Artifacts↗

Determination of dysprosium in monkey serum by inductively-coupled plasma atomic emission spectrometry (ICP-AES) after the administration of Sprodiamide Injection, a new contrast medium for magnetic resonance imaging.

Sprodiamide Injection (S-043 Injection, Nycomed Salutar; WIN 59080, Sterling Winthrop) is a magnetic susceptibility-based MRI contrast agent which contains 500 mM dysprosium diethylenetriaminepentaacetic acid bis(methylamide) (DyDTPA-BMA), and 25 mM caldiamide sodium (CaNaDTPA-BMA). A study was conducted to evaluate clearance of drug in cynomolgus monkeys. Eighteen cynomolgus monkeys, divided into three groups of six animals each, were administered Sprodiamide Injection intravenously at dose levels of 0.25, 0.5 and 2.5 mmol kg-1, respectively. The concentration of dysprosium in serum was determined in a monkey serum-hydrochloric acid matrix by inductively-coupled plasma atomic emission spectrometry (ICP-AES). The ICP-AES method was demonstrated to be valid for sensitivity, precision, accuracy, and specificity. The dynamic range was linear from 0 to 50 micrograms ml-1 and the limit of quantification was 24 ng ml-1. The measured dysprosium concentration in monkey serum ranged from 0 to 339 micrograms ml-1 for the 0.25 mmol kg-1 Sprodiamide Injection dose group, from 0 to 633 micrograms ml-1 for the 0.5 mmol kg-1 and from 0 to 2920 micrograms ml-1 for 2.5 mmol kg-1 dose groups. Dysprosium was not detected after 480 min in any of the serum samples from the 0.25 and 0.5 mmol kg-1 dose groups after the administration of Sprodiamide Injection. All the monkeys in the 2.5 mmol kg-1 dose group, with one exception, required 720 min for clearance of the drug from the serum. The drug was completely cleared from serum in all monkeys within 24 h.

Animals↗

Structure of the dysprosium-glycocholate complex in submicellar aqueous solution: paramagnetic mapping by proton nuclear magnetic resonance spectroscopy. An approximation for the intrinsic "bound" relaxation rates in the case of nondilute paramagnetic systems.

A paramagnetic NMR study of the structure of the calcium-glycocholate complex in submicellar solution, utilizing dysprosium as an isomorphous lanthanide replacement of calcium, is presented. The dysprosium-induced relaxation rate (1/T1) enhancements of certain glycocholate protons have been used to estimate internuclear distances between these protons and the metal ion. An approximation to calculate the intrinsic relaxation rate (1/T1) enhancements for a nondilute paramagnetic solution is given in the Appendix. From these data, and analysis based on conformation averaging and minimum energy conformations, a molecular model of the dysprosium-glycocholate complex in submicellar aqueous solution has been constructed. In this model the metal ion has a unidentate, first-sphere interaction with the proximal oxygen atom of the glycine carboxyl. The metal ion has second-sphere interactions with the peptide bond carbonyl oxygen (3.6 A) and the distal carboxyl oxygen (4.4 A). The metal ion to hydroxyl oxygen distances (8.4-12.4 A) are not compatible with any metal ion to hydroxyl coordination. The side chain appears to exist in one predominant conformation. All six oxygen atoms of glycocholate, the peptide bond carbonyl, the carboxyl group, and the hydroxyl groups are on the alpha face of the bile salt molecule. On the basis of these features we conclude that in the submicellar state the solution structure of the dysprosium-glycocholate complex displays a metal ion enhanced segregation of polar versus nonpolar groups to the two separate faces of the molecule, which may result in a facilitated hydrophobic interaction of different complex units.

Computer Simulation↗

[Columinescence effect of dysprosium-lanthanum-tiron system and its applicaton].

The columinescence effect of dysprosium-Tiron system by lanthanum was discovered and the characteristics of fluorescence spectra of the system were studied. The effect of the experimental conditions on the fluorescence intensity was defined. By adding suitable amount of lanthanum to dysprosium-Tiron system, the fluorescence intensity can be enhanced by about 40 times. The fluorescence intensity is a linear function of the concentration of dysprosium in the range of 5.0 x 10(-8)-9.0 x 10(-6) mol/L. The detection limit is 1.0 x 10(-10) mol/L. Standard addition method is used for the determination of dysprosium in synthetic rare earth sample with satisfactory results.

English Abstract↗

In vitro and in vivo dissolution behavior of a dysprosium lithium borate glass designed for the radiation synovectomy treatment of rheumatoid arthritis.

Dysprosium lithium borate (DyLB) glass microspheres were investigated for use in the radiation synovectomy treatment of rheumatoid arthritis. In vitro testing focused on weight loss and cation dissolution from glass microspheres immersed in simulated synovial fluid (SSF) at 37 degrees C for up to 64 days. In vivo testing was performed by injecting glass microspheres into the stifle joints of Sprague-Dawley rats and monitoring the biodegradability of the microspheres and the tissue response within the joints. The DyLB microspheres reacted nonuniformly in SSF with the majority of lithium and boron being dissolved, whereas nearly all of the dysprosium (>99.7%) remained in the reacted microspheres. Because the DyLB glasses released negligible amounts of dysprosium while reacting with SSF, they are considered safe for radiation synovectomy from the standpoint of unwanted radiation release from the joint capsule. Furthermore, the DyLB microspheres fragmented, degraded, and reacted with body fluids while in the joints of rats without histologic evidence of joint damage.

Algorithms↗

Comparison of dysprosium DTPA BMA and superparamagnetic iron oxide particles as susceptibility contrast agents for perfusion imaging of regional cerebral ischemia in the rat.

The aim of the study was to compare the first-passage profiles of dysprosium diethylenetriamine penta-acetic acid bis(methylamide) (DTPA BMA) and the superparamagnetic iron oxide particles NSR 0430 in regions with severe and moderate cerebral ischemia. In seven rats subjected to middle cerebral artery occlusion, two dynamic MR perfusion imaging series were acquired after intravenous bolus injections of .5 mmol/kg dysprosium DTPA BMA and .06 mmolFe/kg iron oxide particles, respectively. The doses were chosen to obtain similar maximum signal change in normally perfused brain. The first-passage profiles were compared in a region of interest (ROI) in the core area with severe ischemia and in a ROI in the penumbra area of moderate ischemia. The results were compared both as the calculated mean signal intensity versus time curves for all seven rats and statistically for an estimated mean transit time (MTT) after gamma variate fitting of the calculated concentration versus time curves. The first-passage profiles for the two contrast agents were similar, both in the core area of severe ischemia and in the penumbra area of moderate ischemia. In this rat stroke model, dysprosium DTPA BMA and the superparamagnetic iron oxide particles NSR 0430 were found to be equally efficacious for the diagnosis of the perfusion deficit, but if safe for human investigations, iron oxide particles would have an advantage as equal susceptibility effect may be achieved with smaller injection volumes.

Animals↗

Simultaneous determination of dysprosium and iron in urine by capillary zone electrophoresis coupled to cloud point extraction.

Automated preconcentration strategies are needed when analyzing metals in real samples by capillary electrophoresis (CE) with UV detection. The on-line incorporation of cloud point extraction (CPE) to flow injection analysis (FIA) associated with CE for simultaneously determining dysprosium and iron at ppb levels in urine is presented and evaluated for the first time. The preconcentration step is mediated by micelles of the non-ionic surfactant polyethyleneglycol-mono-p-nonylphenylether (PONPE 7.5) with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol. The micellar system containing the complex was loaded into the FIA manifold at a flow rate of 8 mlmin(-1), and the surfactant rich-phase was retained in a microcolumn packed with cotton, at pH 9.2. The surfactant-rich phase was eluted with 50 microl acetonitrile directly into the CE sample vial, allowing to reach an enrichment factor of 200-fold for a 10 ml sample urine. The type and composition of the background electrolytes (BGE) were investigated with respect to separation selectivity, reproducibility and stability. A BGE of 20mM sodium tetraborate buffer containing 13% acetonitrile, pH 9.0 was found to be optimal for the separation of metal chelates. Detection was performed at 585 nm. An enhancement factor of 200 was obtained for the preconcentration of 10 ml of sample solution. The detection limits for the preconcentration of 10 ml of urine were 0.20 microgl(-1) for Dy, and. 0.48 microgl(-1) for Fe. The calibration graphs using the preconcentration system were linear with a correlation coefficient of 0.9989 (Dy) and 0.9976 (Fe) at levels near the detection limits up to at least 500 microgl(-1). The method was successfully applied to the determination of dysprosium and iron in urine for monitoring the elimination of dysprosium-based pharmaceuticals.

Dysprosium↗

Magnetophoretic velocity of microorganic droplets adsorbed by dysprosium(III) laurate in water.

By using an improved apparatus for the observation of magnetophoresis, the magnetophoretic velocity of 2-fluorotoluene droplets including lauric acid was measured in aqueous dysprosium(III) solution. The magnetophoretic velocity of pure 2-fluorotoluene droplets was proportional to the square of the radius. On the other hand, the velocity of the organic droplets including lauric acid in the dysprosium(III) solution showed a deviation from the square radius relationship, more remarkably in smaller droplets than 2 microm in radius. These results indicated that the dysprosium(III)-laurate complex was formed at the liquid-liquid interface. This study is the first report on the detection of the interfacial complex by the magnetophoresis of the microdroplet.

Adsorption↗

Synovectomy of the rheumatoid knee using intra-articular injection of dysprosium-165-ferric hydroxide macroaggregates.

One hundred and eleven patients who had seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with intra-articular injection of 270 millicuries of dysprosium-165 bound to ferric hydroxide macroaggregates. A two-year follow-up was available for fifty-nine of the treated knees. Thirty-nine had a good result; nine, a fair result; and eleven, a poor result. Of the twenty-five knees that had Stage-I radiographic changes, nineteen had a good result. Of the thirty-four knees that had Stage-II radiographic changes, twenty showed a good result. Systemic spread of the radioactivity from the injected joint was minimum. The mean whole-body dose was calculated to be 0.3 rad and that to the liver twenty-four hours after injection, 3.2 rads. The results indicated that dysprosium-165-ferric hydroxide macroaggregate is an effective agent for performing radiation synovectomy, particularly in knees that have Stage-I radiographic changes. Because of the minimum rate of systemic spread of the dysprosium-165, it offers a definite advantage over agents that previously have been used.

Adult↗

Magnetic interactions between dysprosium complexes and two soluble iron-sulfur proteins.

A tetranuclear ferredoxin from Rhodopseudomonas gelatinosa [4Fe-4S](+2,+3) has been examined by electron paramagnetic resonance techniques. The temperature-dependence and relaxation characteristics of the spectral lines indicate that the spin-lattice interaction is described at low temperatures by a T2 law which gives way to a T9 Raman relaxation as the temperature is raised. At higher temperatures an Orbach process becomes dominant. In the presence of dysprosium complexes the relaxation and line widths are modified. From crystallographic structure determinations of similar proteins we are able to relate the dysprosium effects to the spatial separation between the complex and the tetranuclear cluster. This scale is then tested against a ferredoxin from Clostridium pasteurianum which contains two tetranuclear clusters, [4Fe-4S](+1,+2). We find that for these soluble iron-sulfur proteins the dysprosium complexes form a shell at the protein surface. The magnetic interaction between the clusters and the complexes altering the relaxation time goes as r-6, while the low temperature line broadening is described by an r-3 dipole interaction.

Clostridium↗

[Use of dysprosium considered as an activable tracer in the study of tooth structures].

After 32 days of administration to rats of dysprosium in drinking water, this element has been studied by neutron activation analysis in the intra-oral part of the incisors as well as in the molar crowns. This element was absent in the intra-osseous parts of the incisors, the femurs and the liver. After intravenous injection of 13 mg or 26 mg of Dy in several doses over 32 days, this element was found in the incisor formation and maturation zones as well as in the part having erupted in the oral cavity. It was also found in the molars, the femurs and the liver. The structural study has shown that no cytotoxic effect was observed with the dysprosium doses used. Dentinogenesis and amelogenesis were not disturbed. The final structures were homogeneous. By comparing the two administration ways of dysprosium we have at our disposal a study model using an inducible tracer of the incorporation of adsorption of a mineral element in dental structures during early or late maturations.

Animals↗

[Fluorescence enhancement of the dysprosium-sulfosalicylic acid system by lanthanum and its application].

A fluorescence enhancement produced by adding lanthanum(III) to dysprosium-sulfosalicylic acid system was observed. La3+ enhanced the fluorescence intensity by two orders of magnitude compared with the system without La3+. The system was used for the determination of trace amount of dysprosium in the range of 3.0 x 10(-7)-1.0 x 10(-5) mol/dm3, and the detection limit was 8.0 x 10(-8) mol/dm3. The procedure was applied to the determination of dysprosium in synthetic rare earth samples and standard rare earth samples with satisfactory results.

English Abstract↗