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Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium 165-ferric hydroxide macroaggregates.

One hundred eight knees of 93 patients with seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with an intraarticular injection of 270 mCi of dysprosium 165 bound to ferric hydroxide macroaggregate. Leakage of radioactivity from the injected joint was minimal. Mean leakage to the venous blood 3 hours after injection was 0.11% of the injected dose; this corresponds to a mean whole body dose of 0.2 rads. Mean leakage to the liver 24 hours after injection was 0.64% of the injected dose; this corresponds to a mean liver dose of 3.2 rads. In 7 additional patients examined, there was negligible or near negligible activity found in the draining inguinal lymph nodes. One-year followup was possible for 74 knees (63 patients). Sixty-one percent of the knees had good results, 23% had fair results, and 16% had poor results. There was a direct correlation between the radiographic stage and response to treatment. In knees with stage I radiographic changes, 72% showed good results; 93% showed improvement. In knees with stage II changes, 59% showed good results; 81% showed improvement. These preliminary results indicate that dysprosium 165-ferric hydroxide macroaggregate is an effective agent for radiation synovectomy. The low leakage rates observed offer a definite advantage over agents previously used.

Adult↗

Molecular factors that determine Curie spin relaxation in dysprosium complexes.

Dysprosium complexes can serve as transverse relaxation (T(2)) agents for water protons through chemical exchange and the Curie spin relaxation mechanism. Using a pair of matched dysprosium(III) complexes, Dy-L1 (contains one inner-sphere water) and Dy-L2 (no inner-sphere water), it is shown that the transverse relaxation of bulk water is predominantly an inner-sphere effect. The kinetics of water exchange at Dy-L1 were determined by (17)O NMR. Proton transverse relaxation by Dy-L1 at high fields is governed primarily through a large chemical shift difference between free and bound water. Dy-L1 forms a noncovalent adduct with human serum albumin which dramatically lengthens the rotational correlation time, tau(R), causing the dipole-dipole component of the Curie spin mechanism to become significant and transverse relaxivity to increase by 3-8 times that of the unbound chelate. These findings aid in the design of new molecular species as efficient r(2) agents.

Contrast Media↗

Reactions of dysprosium with adenine nucleotides.

Dysprosium catalyzes a rapid hydrolysis of both ATP and ADP, at ambient temperatures, pH 7.0, where no hydroxide precipitates. The reactive complexes, at pH 6.7, were found to contain 2Dy:1ATP and 3Dy:2ADP. AMP forms an insoluble complex containing 1Dy:2AMP, which does not hydrolyze. ATP also forms a soluble 1Dy:1ATP complex, which does not react. Dysprosium only catalyzes the hydrolysis of ATP above pH 5.8, where it has been titrated to the hydroxide. At the optimum pH (pH 7) the stoichiometric composition is Dy2.ATP.(OH)2, indicating that the active complex is neutral, whereas at pH 5.8 the stoichiometric composition is Dy2.ATP.(OH)+, indicating an inactive cationic complex. The mechanism proposed for the hydrolysis is consistent with those proposed for other in vitro systems known to catalyze the hydrolysis of ATP.

Adenine Nucleotides↗

Dysprosium(III) hydroxide coprecipitation system for the separation and preconcentration of heavy metal contents of table salts and natural waters.

A procedure for the determination of trace amounts of Pb(II), Cu(II), Ni(II), Co(II), Cd(II) and Mn(II) is described, that combines atomic absorption spectrometry-dysprosium hydroxide coprecipitation. The influences of analytical parameters including amount of dysprosium(III), centrifugation time, sample volume, etc. were investigated on the recoveries of analyte ions. The effects of concomitant ions were also examined. The recoveries of the analyte ions were in the range of 95.00-104.00%. The detection limits corresponding to three times the standard deviation of the blank for the analytes were in the range of 14.1-25.3 microg/L. The method was applied to the determination of lead, copper, nickel, cobalt, cadmium and manganese ions in natural waters and table salts good results were obtained (relative standard deviations <10%, recoveries >95%).

Centrifugation↗

Determination of dysprosium by resonance light scattering technique in the presence of BPMPHD.

Dysprosium has been determined by resonance light scattering (RLS) method in the presence of 1,6-bi(1'-phenyl-3'-methyl-5'-pyrazolone-4'-)hexanedione (BPMPHD) at pH 5.5. The Dy-BPMPHD system has three characteristic peaks at 358, 399 and 450 nm, especially the peak at 358 nm, which is proportional to the concentration of Dy(3+) in the range of 1.0 x 10(-10)-1.0 x 10(-5) mol l(-1). The detection limit (S/N=2) is 5.6 x 10(-12) mol l(-1). Synthetic samples are determined satisfactorily. A new sensitive method for detection of dysprosium has been proposed.

Animals↗

Using dysprosium complexes to probe the nitrogenase paramagnetic centers.

EPR progressive power saturation techniques were used to monitor relaxation enhancement of the nitrogenase paramagnetic centers produced by interaction with Dy3+ complexes. Three models are presented for the relationship between the degree of enhancement and the distance of closest approach of Dy3+ to the intrinsic metal cluster. In the first model, the perturbing dysprosium ions are represented as a single average site. The second and third models are variations of the treatment of Innes and Brudvig [(1989) Biochemistry 28, 1116-1125] and assume the unknown protein to be spherical with Dy3+ dispersed either randomly over the surface of the protein or randomly in solution. Using these models, the distance of closest approach of the Dy3+ complex to the [4Fe-4S] cluster in the Fe-protein from Azotobacter vinelandii was determined to be 5.0-6.5 A. Similarly, the distance of closest approach to FeMoco in the MoFe-protein was determined to be 0.0-1.2 A, which, when corrected to the fact that FeMoco exists as an S = 3/2 spin state, indicates that the distance is > or = 6 A. These distances did not change when (1) either protein was in the presence of the other, (2) both proteins were cross-linked to each other, or (3) the Fe-protein from A. vinelandii was mixed with the MoFe-protein from Clostridium pasteurianum. On the other hand, formation of the inactive complex of the Fe-protein from C. pasteurianum with the MoFe-protein from A. vinelandii blocked dysprosium-induced relaxation enhancement, implying that each component protein overlaps the metal cluster in the complementing protein.

Azotobacter vinelandii↗

Dysprosium-enhanced MR imaging for tumor tissue characterization. An experimental study in a human xenograft model.

PURPOSE: To evaluate dysprosium-enhanced MR imaging for differentiation between morphologically intact and necrotic tumor tissue in a tumor model. MATERIAL AND METHODS: A human colon carcinoma was transplanted subcutaneously into 9 nude (immunodeprived) rats. MR imaging was performed before and after injection of the dysprosium agent Dy-DTPA-BMA. T1-, T2- and T2*-weighted sequences were acquired. The tumors were dissected, histological sections were prepared, and compared with corresponding MR images. RESULTS: In intact tissue, the MR signal intensity in the T2- and T2*-weighted images decreased after Dy injection and the delineation of the intact regions were sharp and corresponded well to the gross histological sections. CONCLUSION: Dy-enhanced MR imaging facilitated the differentiation between intact and necrotic tumor tissue.

Adenocarcinoma↗

Histochemistry of sarcoplasmic reticulum Ca-ATPase using dysprosium as capturing reagent.

This report describes the development of a histochemical method for the demonstration of sarcoplasmic reticulum Ca-ATPase activity in cross-sections of skeletal muscle. The demonstration of sarcoplasmic reticulum Ca-ATPase activity is complicated by the fact that capturing reagents for phosphate inhibit the enzyme. We present a minimal model for heavy-metal-phosphate precipitation reactions which gives a theoretical description of the effect of enzyme inhibition on the rate of phosphate precipitation in the section. The model indicates that the choice of capturing reagent is crucial: whether or not ATPase activity can be demonstrated depends mainly on the inhibition constant and the solubility product of the phosphate salt of the capturing reagent (but also on a fairly large number of other factors). All lanthanides tested can be used to demonstrate sarcoplasmic reticulum Ca-ATPase activity, but dysprosium results in the highest staining intensity. This suggests that dysprosium inhibits sarcoplasmic reticulum Ca-ATPase to a lesser degree than the other lanthanides and/or the solubility product of its phosphate salt is smaller. As an example, the method is used to investigate the effect of thyroid hormone on sarcoplasmic reticulum Ca-ATPase activity in individual fibres of the rat soleus muscle.

Animals↗

Dosimetry of in situ activated dysprosium microspheres.

This paper presents the results of a study aimed at investigating the dosimetry of stable dysprosium microspheres activated, in situ, by a linac generated photon beam. In phantom measurements of the neutron flux within an 18 MV photon beam were performed using CR-39 detectors and gold activation. The results were used in conjunction with a Monte Carlo computer simulation to investigate the dose distribution resulting from the activation of dysprosium (Dy) microspheres using an 18 MV photon beam. Different depths, lesion volumes and volume concentrations of microspheres are investigated. The linac lower collimator jaws are assumed completely closed to shield the tumour volume from the photon dose. Using a single AP field with 0 x 0 cm2 field size (closed jaws), a photon dose rate of 600 MU min(-1) and 80 cm SSD for 10 min, an average dose exceeding 1 Gy can be delivered to spherical lesions of 0.5 cm and higher diameter. The variation of the average dose with the size of the lesion reaches saturation for tumour volumes exceeding 1 cm in diameter. This report shows that the photon beam of a high-energy linac can be used to activate Dy microspheres in situ and, as a result, deliver a significant dose of beta radiation. Non-radioactive Dy microspheres do not have the toxicity and imaging problems associated with commercially available yttrium-90 based products.

Dose-Response Relationship, Radiation↗

Ordered charge asphericity around dysprosium and structural deformation in DyB2C2.

The orbitally ordered phase of DyB2C2 has been studied by nonresonant x-ray diffraction with high-brilliance synchrotron radiation. From the condition of diffraction, the symmetry property of the charge distribution around dysprosium has been concluded at the quadrupolar level. The quantitative inspection, furthermore, indicates that the observed signals cannot be interpreted as arising only from the 4f electrons of dysprosium responsible for the ordering; instead, the experiment can be described rather well by considering a distortion of the metaloid network concomitant with the ordering.

Journal Article↗

Treatment of psoriasis with trioxsalen baths and dysprosium lamps.

Photochemotherapeutic treatment of psoriasis with trioxsalen baths (0.5 mg/1) for 15 minutes followed by irradiation with dysprosium lamps (Osram HQI-TS) healed or nearly healed the psoriatic lesions in 18 patients within 3-5 weeks. A control area treated with the Ingram method showed a slower healing in 9 of these patients. Methoxsalen bath was not as effective in healing at the concentration used (1 mg/l). The bath method is easy to administer and cosmetically acceptable. Sensitisation to light is maximal immediately after the bath and disappears more quickly than after painting with an alcoholic trioxsalen solution. By using baths, there is less risk of accidental burns or uneven pigmentation than with the often time-consuming local application of psoralen solutions. Toxic systemic effects, which are possible with oral treatment, are less apt to occur. The dysprosium lamps give high intensity in the UV-A region. Exposure times of 10 seconds to 8 minutes are effective in the treatment of psoriasis, where both the UV-B region itself and the UV-A in combination with trioxsalen have psoriasis-healing properties.

Adolescent↗

Repeat radiation synovectomy with dysprosium 165-ferric hydroxide macroaggregates in rheumatoid knees unresponsive to initial injection.

Because of failure to fully respond to an initial intraarticular injection of dysprosium 165-ferric hydroxide macroaggregates, 17 patients with seropositive rheumatoid arthritis underwent repeat radiation synovectomy using this agent. Of the 13 patients who were evaluated 1 year later, 54% (7 knees) had good results, 31% (4 knees) had fair results, and 15% (2 knees) had poor results. The initial lack of significant benefit from radiation synovectomy did not appear to preclude a favorable response to a second injection.

Adult↗

Treatment of antigen-induced arthritis in rabbits with dysprosium-165-ferric hydroxide macroaggregates.

Dysprosium-165-ferric hydroxide macroaggregates (165Dy-FHMA) was used as an agent of radiation synovectomy in an antigen-induced arthritis model in New Zealand white rabbits. Animals were killed up to 6 months after treatment. 165Dy-FHMA was found to have a potent but temporary antiinflammatory effect on synovium for up to 3 months after treatment. Treated knees also showed significant preservation of articular cartilage architecture and proteoglycan content compared with untreated controls, but only during the first 3 months after treatment. In animals killed 3 and 6 months after treatment there were only minimal differences between the treated and untreated knees, indicating that the antiinflammatory effects on synovial tissue and articular cartilage preservation were not sustained.

Animals↗

Gadolinium and dysprosium chelates of DTPA-amide-dextran: synthesis, 1H NMR relaxivity, and induced 23Na NMR shift.

In this study the conjugated macromolecular ligand, diethylenetriaminepentaacetic acid (DTPA)-amide-dextran, was synthesized by attaching DTPA to the dextran macromolecule (M(r) approximately 6000) by a covalent amide bond. Subsequently, DTPA-amide-dextran was complexed with either of the two lanthanide metal ions dysprosium (Dy) or gadolinium (Gd). The paramagnetic 23Na NMR shift induced by Dy(DTPA-amide-dextran) and the relaxivity (rho 1) induced by Gd(DTPA-amide-dextran) were characterized. Dy(DTPA-amide-dextran) induced a 25% larger 23Na NMR shift than that induced by Dy(DTPA). Neither the shift induced by Dy(DTPA-amide-dextran) nor the shift induced by Dy(DTPA) was affected by increasing levels of calcium ions in the solution. offDTPA-amide-dextran) exhibited an in vitro rho 1 of 8.4 (mM s)-1 at a 0.23 T magnetic field and 9.3 (mM s)-1 at a 0.47 T magnetic field, thus indicating a positive magnetic field dependence.

Amides↗

Monitoring of the biodistribution and biokinetics of dysprosium-165 ferric hydroxide with a shadow-shield whole-body counter.

Radiation synovectomy is indicated when conventional pharmacological treatment of chronic synovitis has proved insufficient. In these cases dysprosium-165 ferric hydroxide (DFH) has been demonstrated to be clinically effective. After application of the agent, blood activity measurements and monitoring of activity distribution by gamma camera imaging over the local lymph nodes and the liver are commonly performed for control of possible leakage. In addition, we have used a shadow-shield whole-body counter with a profile facility to evaluate the biokinetics and biodistribution of 165Dy-DFH. Fifteen intra-articular injections were performed in 13 patients who received a median activity of 6.8 GBq (range 0.5-9.9 GBq) 165Dy-DFH. Activity profiles were obtained with the whole-body counter 2, 4 and 6 h after injection of 165Dy-DFH. The doses to non-target organs were calculated using the software MIRDOSE 3. In 10 of 15 treatments, absence of any leakage could be demonstrated. The effect of scattered rays could be observed in 14 measurements. In three patients small amounts of activity could be detected in the urinary bladder and in three patients activity was detected in the local inguinal lymph nodes, while no leakage could be detected by camera imaging. In these cases the individual doses to the bladder were 15 Gy, 65 mGy and 50 mGy, and those to the lymph nodes, 0.54 Gy, 0.89 Gy and 2.41 Gy. The whole-body counter also enabled the monitoring of activity profiles related to more complex pathological structures. In conclusion, using a whole-body counter activity leakage could be detected with much higher sensitivity than by using a gamma camera. The biodistribution of 165Dy-DFH could be determined, and leakage could be localised and related to organs. These results encourage the use of a whole-body counter to identify the site and extent of activity leakage.

Adult↗

Detection of reperfused ischemia of the rat intestine: value of magnetic resonance imaging with small-molecular-weight dysprosium and gadolinium chelates.

RATIONALE AND OBJECTIVES: The authors assessed whether the small-molecular-weight magnetic resonance (MR) imaging contrast agents dysprosium diethylenetriamepentaacetic acid bismethylamide (sprodiamide injection), which enhances T2*, and gadolinium diethylenetriamepentaacetic acid bismethylamide (gadodiamide injection), which enhances T1, could improve the detection of reperfused ischemia of the rat intestine. METHODS: Eighteen rats were subjected to vascular occlusion of the distal ileum for 30 minutes, followed by reperfusion. Ten minutes after reperfusion, T1- and T2-weighted spin-echo (SE) images were obtained before and after administration of sprodiamide, gadodiamide, or both. The same imaging protocol was applied in another group of 18 rats subjected to 10 minutes of occlusion and reperfusion. Histologic examination of the intestine was performed after MR imaging. RESULTS: Villous injury (ie, denudation) was observed in most cases after 30 minutes of occlusion, but not after 10 minutes of occlusion. After 30 minutes of occlusion, the superficial part of the ischemic intestine was hyperintense to the normal intestine on unenhanced T2-weighted images. Administration of sprodiamide improved the contrast between the normal and ischemic intestine on T2-weighted images, and administration of both gadodiamide and sprodiamide improved the contrast on T1- and T2-weighted images. After 10 minutes of occlusion, no contrast was discernible before or after contrast material administration. CONCLUSION: These results suggest that the detection of reperfused intestinal ischemia of sufficient duration to cause villous injury can be improved by using sprodiamide injection alone or in combination with gadodiamide.

Animals↗

Kinetics of [103Ru]phenanthroline and dysprosium particulate markers in the rumen of steers.

Two rumen cannulated steers consuming 5.5 kg air-dry lucerne (Medicago sativa) hay/d given at two-hourly intervals were used to study the kinetics in the rumen of the two particulate markers, 103Ru-labelled Tris-(1, 10-phenanthroline) ruthenium II chloride ([103Ru]P) and dysprosium (Dy). Provision of markers was achieved by allowing the steers to eat separated stems of the hay on to which had been sprayed solutions of the markers. The intake of large-particle (retained by a 3.2 mm mesh screen) dry matter (DM) in boluses and the rumen large-particle pool size measured by emptying the rumen were used to calculate the turnover rate-constant of this pool (1.02 and 1.19/d for steers A and B respectively). The decline with time of both [103Ru]P and Dy associated with large-particle DM in raft digesta was best described by two-compartmental kinetics. The first compartment apparently reflected a combination of the processes of mixing of labelled particles throughout the rumen contents, physical migration of marker from the labelled hay, and physical breakdown of large particles to small particles. The disappearance with time of [103Ru]P and Dy associated with small particles from the raft, ventral digesta and faeces from 3 to 8 d was well described by a single kinetic compartment with a rate constant similar to that of the second compartment of the large particles from the raft. [103Ru]P was rapidly distributed through both the raft and ventral digesta of the rumen. This observation, taken together with measurements of migration of [103Ru]P, suggested that on entering the rumen much of the [103Ru]P did not remain associated with the original feed material. The majority (63-64%) of Dy entered the raft digesta and mixed only slowly through the rumen contents. Some Dy (18-27%) apparently migrated rapidly from large particles and to small particles immediately after ingestion and there was also evidence for some slow migration from small to large particles. When used under the conditions described for this experiment neither [103Ru]P nor Dy was satisfactory as a marker to trace the passage through the rumen of a particular meal.

Animal Feed↗

Dietary inulin intake and age can significantly affect absorption of the faecal marker dysprosium in rats.

It is believed that rare earth elements are not absorbed, and thus they are generally used in some mineral absorption studies as a faecal marker. The aim of the present study was to determine the effect of inulin intake and age on dysprosium (Dy) absorption in rats. Eighty male Wistar rats of four different ages (2, 5, 10 and 20 months) were randomised into either a control group or a group receiving 3.75 % inulin in their diet for 4 d and then 7.5 % inulin until the end of the study. The animals were fed fresh food and water ad libitum for 30 d. The intestinal absorption of Dy was determined from a 4 d (day 21 to day 25) balance study. Mean faecal Dy recovery (%) in the eight groups (3 months control, 3 months inulin, 6 months control, 6 months inulin, 11 months control, 11 months inulin, 21 months control, 21 months inulin) was 94.0 (sd 8.6), 64.8 (sd 10.1), 95.8 (sd 9.4), 81.5 (sd 12.1), 98.4 (sd 9.8), 87.8 (sd 9.5), 97.8 (sd 6.2) and 84.9 (sd 10.9), respectively. Our results showed clearly that dietary inulin intake decreased faecal Dy recovery in all four rat groups, and faecal Dy recovery was significantly higher in the old rats (10 and 20 months) than in the young and adult rats. These results show that the faecal recovery (or intestinal absorption) of Dy may vary greatly with nutritional or physiological states such as inulin intake or age. The use of rare earth elements as a faecal marker should be thus validated under each nutritional or physiological state before being employed in mineral absorption studies.

Age Factors↗