Gadopentetic Acid Research Articles

Cerebral sparganosis in children: epidemiological, clinical and MR imaging characteristics

BackgroundCerebral sparganosis in children is an extremely rare disease of central nervous system, and caused by a tapeworm larva from the genus of Spirometra. In this study, we discussed and summarized epidemiological, clinical and MR imaging characteristics of eighteen children with cerebral sparganosis for a better diagnosis and treatment of the disease.MethodsEighteen children with cerebral sparganosis verified by pathology, serological tests and MR presentations were retrospectively investigated, and the epidemiologic and clinical characteristics of the disease were studied.ResultsTwenty-seven lesions were found in the eighteen children. Twelve lesions in twelve patients were solitary while the lesions in the rest six patients were multiple and asymmetrical. The positions of the lesions were: seven in frontal, eleven in parietal, four in temporal and two in occipital lobes, one in basal ganglia, one in cerebella hemisphere and one in pons. The lesions were presented as slight hypointensity on T1-weighted images but moderate hyperintensity on T2-weighted images with perilesional brain parenchyma edema. Enhanced MR scans by using Gadopentetic Acid Dimeglumine Salt were performed in the patients, and the images demonstrated abnormal enhancements with the patterns of a peripheral ring, or a tortuous beaded, or a serpiginous tubular shape. Follow-up MR scans were preformed for eight patients, and three out of the eight cases exposed migrations and changes in shapes of the lesion areas.ConclusionsThe MR presentations in our study in general were similar to those in previous studies. However serpiginous tubular and comma-shaped enhancements of lesions have not been previously reported. The enhanced MR imaging and follow-up MR scans with the positive results from serological tests are the most important methods for the clinical diagnosis of cerebral sparganosis in children.

In Vivo Characterization of Changing Blood-Tumor Barrier Permeability in a Mouse Model of Breast Cancer Metastasis

The current lack of efficacy for any chemo- or molecular therapeutic in the treatment of brain metastases is thought to be due, in part, to the heterogeneous permeability of the blood-brain-barrier (BBB). Little is known about how heterogeneous permeability develops, or how it varies among individual metastases. Understanding the BBB's role in metastasis will be crucial to the development of new, more effective therapies. In this article, we developed the first magnetic resonance imaging-based strategy to detect and measure the volumes of BBB permeable and nonpermeable metastases and studied the development of altered BBB permeability in metastases in vivo, over time in a mouse model of breast cancer metastasis to the brain. Animals bearing human experimental brain metastases of breast cancer (231-BR cells) were imaged, using 3-dimensional balanced steady-state free precession to visualize total metastases, and contrast-enhanced T1-weighted spin echo with gadopentetic acid (Gd-DTPA) to visualize which of these displayed contrast enhancement, as Gd-DTPA leakage is indicative of altered BBB permeability. Metastases detected 20 days after injection showed no Gd-DTPA enhancement. At day 25, 6.1% ± 6.3% (mean ± standard deviation) of metastases enhanced, and by day 30, 28.1% ± 14.2% enhanced (P < 0.05). Enhancing metastases (mid: 0.14 ± 0.18 mm, late: 0.24 ± 0.32 mm) had larger volumes than nonenhancing (mid: 0.04 ± 0.04 mm, late: 0.09 ± 0.09 mm, P < 0.05); however, there was no significant difference between the growth rates of the 2. A significant number of brain metastases were uniformly nonpermeable, which highlights the need for developing treatment strategies that can overcome the permeability of the BBB. The model developed herein can provide the basis for in vivo evaluation of both BBB permeable and nonpermeable metastases response to therapy.

In vitro effects of some drugs on human erythrocyte glutathione reductase

The effects of ketotifen, meloxicam, phenyramidol–HCl and gadopentetic acid on the enzyme activity of GR were studied using human erythrocyte glutathione reductase (GR) enzymes in vitro. The enzyme was purified 209-fold from human erythrocytes in a yield of 19% with 0.31 U/mg. The purification procedure involved the preparation of haemolysate, ammonium sulphate precipitation, 2′′,5′-ADP Sepharose 4B affinity chromatography and Sephadex G-200 gel filtration chromatography. Purified enzyme was used in the in vitro studies. In the in vitro studies, IC50 values and Ki constants were 0.012 mM and 0.0008 ± 0.00021 mM for ketotifen; 0.029 mM and 0.0061 ± 0.00127 mM for meloxicam; 0.99 mM and 0.4340 ± 0.0890 mM for phenyramidol–HCl; 138 mM and 28.84 ± 4.69 mM for gadopentetic acid, respectively, showing the inhibition effects on the purified enzyme. Phenyramidol–HCl showed competitive inhibition, whereas the others showed non-competitive inhibition.

Comparison of gadopentetic acid (Gd-DTPA) and bromide in a dual-tracer field experiment

At a test site consisting of a storage pond and connected artificial aquifer, the long-time behaviour of gadopentetic acid (Gd-DTPA) was compared with the classic tracer bromide (Br–) in a 70-day dual-tracer experiment. The mixed tracer solution was injected into the oligotrophic pond, which is separated from the aquifer by an infiltration bank. The water drained from the aquifer was returned to the pond together with additional fresh groundwater, causing reduced concentrations of Gd-DTPA and Br– in the system. Transmetallation of Gd-DTPA by rare earth elements and yttrium was negligible but Cu2+ and Ni2+ might have played a role. Adsorption and/or biodegradation of Gd-DTPA were negligible. The decline of Gd-DTPA/Br ratios by 18% in the pond over 68 days was caused by reversible sorption of Br– in the aquifer, which caused variation of Br– background. Thus, Br– behaves less conservatively than Gd-DTPA in the aquifer. Comparison of both proves the suitability of Gd-chelates as tracers in hydrological studies. The advantage of Gd-DTPA as a tracer is that natural Gd3+ in water can continuously be monitored by analysing the suite of naturally occurring rare-earth elements. Thus, stable organic Gd-chelates are determinable with high precision at very low concentrations.

Effects of some drugs on human erythrocyte 6-phosphogluconate dehydrogenase: an in vitro study

The inhibitory effects of some drugs on 6-phosphogluconate dehydrogenase from human erythrocytes have been investigated. For this purpose, initially, erythrocyte 6-phosphogluconate dehydrogenase was purified 3364 times in a yield of 58% by using ammonium sulfate precipitation and 2′,5′-ADP Sepharose 4B affinity gel. A temperature of +4°C was maintained during the purification process. Enzyme activity was determined with the Beutler method by using a spectrophotometer at 340 nm. This method was utilized for all kinetic studies. Many commonly used drugs were investigated in this study. Some drugs (ketotifen (Ki: 8.3 ± 1.7 μM), dacarbazine (Ki: 10.1 ± 0.7 μM), meloxicam (Ki: 50.9 ± 13.2 μM), furosemide (Ki: 127 ± 37.8 μM), methotrexate (Ki: 136.7 ± 25.3 μM), metochloropramide hydrochloride (Ki: 2.1113 ± 0.6979 mM), ritodrine hydrochloride (Ki: 6.0353 ± 1.2783 mM), and gadopentetic acid (Ki: 73.4 ± 21.9 mM)) inhibited enzyme activity in vitro. Ki constants for the enzyme were found by means of Lineweaver–Burk graphs. All drugs showed non-competitive inhibition. In addition, IC50 values of the drugs were determined by plotting activity percent vs [I].

Self-Assembly of SiO&lt;SUB&gt;2&lt;/SUB&gt;/Gd-DTPA-Polyethylenimine Nanocomposites as Magnetic Resonance Imaging Probes

Controlled self-assembly of organic/inorganic magnetic hybrid materials have important applications in magnetic resonance imaging (MRI). In this study, a widely used polycation polyethylenimine was conjugated with gadopentetic acid (Gd-DTPA) as a gadolinium bearing polyelectrolyte (Gd-DTPA-PEI). Next, multilayers of Gd-DTPA-PEI were coated on silica nanoparticles through layer-by-layer (LbL) self-assembly with polyanions as monitored by dynamic light scattering, zeta-potential, and scanning electron microscopy. The thickness of the multilayer film was estimated from quartz crystal microbalance based on counting frequency change of each adsorbed layer. The magnetic relaxation of SiO2/(Gd-DTPA-PEl/polyanion), core-shell nanocomposite was tested at 1.5 T magnetic field in a clinical MRI scanner, and a 3-fold increase in T1 relaxivity to 15.1 Gd mM(-1)s(-1) was noticed comparing to Gd-DTPA small molecules. Dextran sulfate was coated as the outermost layer on the nanocomposite for better biocompatibility as verified by in vitro cytotoxicity studies. This formulation provides good signal intensity enhancement of mouse liver in vivo with only 1/25 dose of clinical standard at 30 and 60 minutes after intravenous injection. This sensitive imaging probe with unique core-shell structures may find broad applications in cellular and molecular imaging.

Transmetallation of Gd-DTPA by Cu, Y and lanthanides and its impact on the hydrosphere

Abstract The concurrent exchange of REE 3+ and Y 3+ (combined to M 3+ ) and Cu 2+ for Gd 3+ in Gd-DTPA (Gd-diethylenetriaminepentaacetic acid or gadopentetic acid) in the presence of clay is a very slow process if the concentrations of M 3+ , Cu 2+ and Gd-DTPA in solution are in the range of 0.01–22 nmol/L. The kinetics of transmetallation was followed for 1033 h without reaching equilibrium, although the release of metal ions from the clay pool is a fast process. The sum of all newly formed mono-nuclear M-DTPA species is less than the difference [Gd-DTPA o ] − [Gd-DTPA] even after 1033 h but the sum of all derived M-DTPA + Cu-DTPA chelates exceeds this difference indicating that within this time span poly-nuclear chelates of Cu also formed. Formation of CuGd-DTPA chelates is the fastest process followed by formation of less stable MGd-DTPA chelates. With progress of formation of CuGd-DTPA the concentration of Gd-DTPA is lowered and consequently MGd-DTPA decomposes. Furthermore Cu 2+ reacts with MGd-DTPA to form CuM-DTPA. The observed rate constants vary from species to species, whereas the pseudo-first-order-rate constants k M are nearly the same for all lanthanides. The observed rate constant for k Cu exceeds those of k M because Cu concentrations are higher than M. The changes in M speciation under the influence of DTPA are estimated for a typical composition of surface water. Input of Gd-DTPA leaves only La and, to a lesser degree, Ce unaffected by transmetallation. The total concentrations of both Cu and intermediate to heavy REE increase, whereas total Gd decreases because released Gd 3+ is adsorbed by clay minerals. Depending on Cu 2+ and GdL 2− concentrations in natural surface and groundwaters, Gd-DTPA decreases by about 10% within a year. Equilibrium is theoretically reached only after more than 70 a.

Accumulation of MRI contrast agents in malignant fibrous histiocytoma for gadolinium neutron capture therapy

Neutron-capture therapy with gadolinium (Gd-NCT) has therapeutic potential, especially that gadolinium is generally used as a contrast medium in magnetic resonance imaging (MRI). The accumulation of gadolinium in a human sarcoma cell line, malignant fibrosis histiocytoma (MFH) Nara-H, was visualized by the MRI system. The commercially available MRI contrast medium Gd-DTPA (Magnevist ®, dimeglumine gadopentetate aqueous solution) and the biodegradable and highly gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared as MRI contrast agents. The MFH cells were cultured and collected into three falcon tubes that were set into the 3-tesra MRI system to acquire signal intensities from each pellet by the spin echo method, and the longitudinal relaxation time (T1) was calculated. The amount of Gd in the sample was measured by inductively coupled plasma atomic emission spectrography (ICP-AES). The accumulation of gadolinium in cells treated with Gd-nanoCPs was larger than that in cells treated with Gd-DTPA. In contrast, and compared with the control, Gd-DTPA was more effective than Gd-nanoCPs in reducing T1, suggesting that the larger accumulation exerted the adverse effect of lowering the enhancement of MRI. Further studies are warranted to gain insight into the therapeutic potential of Gd-NCT.

Bystander Killing of Malignant Glioma by Bone Marrow–derived Tumor-Infiltrating Progenitor Cells Expressing a Suicide Gene

Adult stem cells are promising cellular vehicles for therapy of malignant gliomas as they have the ability to migrate into these tumors and even track infiltrating tumor cells. However, their clinical use is limited by a low passaging capacity that impedes large-scale production. In the present study, a bone marrow-derived, highly proliferative subpopulation of mesenchymal stem cells (MSCs)-here termed bone marrow-derived tumor-infiltrating cells (BM-TICs)-was genetically modified for the treatment of malignant glioma. Upon injection into the tumor or the vicinity of the tumor, BM-TICs infiltrated solid parts as well as the border of rat 9L glioma. After intra-tumoral injection, BM-TICs expressing the thymidine kinase of herpes simplex virus (HSV-tk) and enhanced green fluorescent protein (BM-TIC-tk-GFP) were detected by non-invasive positron emission tomography (PET) using the tracer 9-[4-[(18)F]fluoro-3-hydroxymethyl)butyl]guanine ([(18)F]FHBG). A therapeutic effect was demonstrated in vitro and in vivo by BM-TICs expressing HSV-tk through bystander-mediated glioma cell killing. Therapeutic efficacy was monitored by PET as well as by magnetic resonance imaging (MRI) and strongly correlated with histological analysis. In conclusion, BM-TICs expressing a suicide gene were highly effective in the treatment of malignant glioma in a rat model and therefore hold great potential for the therapy of malignant brain tumors in humans.

Positive gadolinium anomaly in surface water and ground water of the urban area Berlin, Germany

Rare-earth element (REE) distribution patterns of surface water and commonly also of ground water from industrialised and highly populated areas show anthropogenic gadolinium (Gd) anomalies. They result from the application of organic Gd compounds, such as the derivatives of the gadopentetic acid (Gd-DTPA), as a contrast medium in magnetic resonance imaging. After excretion from the human body, the Gd complex enters the surface water mostly by the effluents of sewage treatment plants. The chemical complex is very stable over at least 6 months under natural conditions. Owing to its anionic state, it is neither adsorbed onto surfaces of abundant clay mineral particles nor by particulate organic matter, both strongly contrasting with the behaviour of the free REE ions. Thus, this complex behaves like a pseudo-natural marker and provides a tool for tracing the mixing of surface and ground water with recycled water, and the infiltration of surface water into aquifers. In urban areas, where water production is commonly based on bank filtration, the anthropogenic Gd of the surface water can be followed to the water production wells. Like boron, δD and δ 18O, Gd can be used as a marker in the estimation of the recycled water fraction in ground water systems. Examples of anthropogenic Gd distribution in surface water, sewage and ground water in Berlin, Germany, are discussed. Mixing ratios of bank filtrates and ground water are estimated.

Anthropogenic Gd in surface water, drainage system, and the water supply of the city of Prague, Czech Republic.

The anthropogenic Gd (Gdant) loads and fluxes of surface- and groundwaters, and of effluents from sewage treatment plants of Prague and its surroundings, have been determined. While passing Prague the Gdant load of the Vltava river increases from 4.5 to 19.2 nmol/m3, which is caused by the effluents of the central sewage treatment plant with a 6 day average of 250 nmol/m3. The Berounka river with its enhanced content doubles the Gdant flux of the Vltava river before entering Prague. All minor creeks draining Prague add less than 3% of the Gdant load in the Vltava river downstream of Prague. The 11-days average of the amount of the administered Gd complexes of the gadopentetic acid (Gd-DTPA), gadobenic acid, and other compounds in Prague's hospitals (22 g-Gdant/d) exceeds the 6 days average of 15 g-Gdant/d in the effluent of the central sewage treatment plant. This strongly indicates uncontrolled losses of sewage from sewers to the groundwater.

In vitro cellular accumulation of gadolinium incorporated into chitosan nanoparticles designed for neutron-capture therapy of cancer

The accumulation of gadolinium loaded as gadopentetic acid (Gd-DTPA) in chitosan nanoparticles (Gd-nanoCPs), which were designed for gadolinium neutron-capture therapy (Gd-NCT) for cancer, was evaluated in vitro in cultured cells. Using L929 fibroblast cells, the Gd accumulation for 12 h at 37°C was investigated at Gd concentrations lower than 40 ppm. The accumulation leveled above 20 ppm and reached 18.0±2.7 (mean±S.D.) μg Gd/10 6 cells at 40 ppm. Furthermore, the corresponding accumulations in B16F10 melanoma cells and SCC-VII squamous cell carcinoma, which were used in the previous Gd-NCT trials in vivo, were 27.1±2.9 and 59.8±9.8 μg Gd/10 6 cells, respectively, hence explaining the superior growth-suppression in the in vivo trials using SCC-VII cells. The accumulation of Gd-nanoCPs in these cells was 100–200 times higher in comparison to dimeglumine gadopentetate aqueous solution (Magnevist ®), a magnetic resonance imaging contrast agent. The endocytic uptake of Gd-nanoCPs, strongly holding Gd-DTPA, was suggested from transmission electron microscopy and comparative studies at 4°C and with the solution system. These findings indicated that Gd-nanoCPs had a high affinity to the cells, probably contributing to the long retention of Gd in tumor tissue and leading to the significant suppression of tumor growth in the in vivo studies that were previously reported.

Dissolved indium and rare earth elements in three Japanese rivers and Tokyo Bay: Evidence for anthropogenic Gd and In

New data on the dissolved (<0.04 μm) rare earth elements (REEs) and In in the Japanese Ara, Tama, and Tone river-estuaries and Tokyo Bay are presented. Unique shale-normalized REE patterns with a distinct positive Gd anomalies and a strong heavy-REE enrichment were seen throughout the data. The dissolved Gd anomaly is caused by local anthropogenic input mainly due to recent use of Gado-pentetic acid as a medical agent for magnetic resonance imaging (MRI) in hospitals. The heavy-REE enrichment may be attributed to fractionation during weathering and transport in the upstream of the rivers, and only partially to removal of light- and middle-REE enriched river colloids by the use of a new ultrafiltration technique. Dissolved In concentrations in the Japanese rivers are extraordinarily high as compared to those in the pristine Chao Phraya river of Thailand reported elsewhere (Nozaki et al., in press). Like Gd, the high dissolved In in the study area can also be ascribed to recent use of In-containing organic compound, In(DTPA) 2− in medical diagnosis. Thus, in the highly populated and industrialized area, dissolved heavy metal concentrations in rivers and estuaries may be significantly perturbed by human activities and the fate of those anthropogenic soluble substances in the marine environment needs to be investigated further.

Anthropogenic gadolinium as a conservative tracer in hydrology

Surface water and in some cases also groundwaters of industrialised and highly populated areas show REE patterns with outstanding positive Gd anomalies. These are formed by using gadopentetic acid (Gd-DTPA) as a contrast medium in magnetic resonance imaging. This Gd complex is very stable under natural conditions. It is an anion and so not adsorbed onto clay mineral surfaces or particulate organic matter, in contrast to free rare earth element (REE) ions ions. Thus, this complex is a pseudo-natural marker, and allows the study of the origin of certain waters and their fate during mixing processes.

Gadolinium neutron-capture therapy using novel gadopentetic acid–chitosan complex nanoparticles: in vivo growth suppression of experimental melanoma solid tumor

The potential of gadolinium neutron-capture therapy (Gd-NCT) for cancer was evaluated using chitosan nanoparticles as a novel gadolinium device. The nanoparticles, incorporating 1200 μg of natural gadolinium, were administered intratumorally twice in mice bearing subcutaneous B16F10 melanoma. The thermal neutron irradiation was performed for the tumor site, with the fluence of 6.32×10 12 neutrons/cm 2, 8 h after the second gadolinium administration. After the irradiation, the tumor growth in the nanoparticle-administered group was significantly suppressed compared to that in the gadopentetate solution-administered group, despite radioresistance of melanoma and the smaller Gd dose than that administered in past Gd-NCT trials. This study demonstrated the potential usefulness of Gd-NCT using gadolinium-loaded nanoparticles.

Chitosan-gadopentetic acid complex nanoparticles for gadolinium neutron-capture therapy of cancer: preparation by novel emulsion-droplet coalescence technique and characterization.

The gadopentetic acid (Gd-DTPA)-loaded chitosan nanoparticles (Gd-nanoCPs) were prepared for gadolinium neutron-capture therapy (Gd-NCT) and characterized and evaluated as a device for intratumoral (i.t.) injection. Gd-nanoCPs were prepared by a novel emulsion-droplet coalescence technique. The effects of the deacetylation degree of chitosan and Gd-DTPA concentration in chitosan medium on the particle size and the gadolinium content in Gd-nanoCPs were examined. In vitro Gd-DTPA release from Gd-nanoCPs was evaluated using an isotonic phosphate-buffered saline solution (PBS, pH 7.4) and human plasma. In vivo Gd-DTPA retention in the tumor after i.t. injection of Gd-nanoCPs was estimated on mice bearing s.c. B16F10 melanoma. Gd-nanoCPs with the highest Gd content, which were obtained using 100% deacetylated chitosan in 15% Gd-DTPA aqueous solution, were 452 nm in diameter and 45% in Gd-DTPA content. A lower deacetylation degree of chitosan led to an increase in particle size and a decrease in Gd-DTPA content in Gd-nanoCPs. As Gd-DTPA concentration in the chitosan solution increased, Gd-DTPA content in Gd-nanoCPs increased but the particle size did not vary. Gd-DTPA loaded to Gd-nanoCPs was hardly released over 7 days in PBS (1.8%) despite the high water solubility of Gd-DTPA. In contrast, 91% of Gd-DTPA was released in plasma over 24 hours. When Gd-nanoCPs were i.t. injected, 92% of Gd-DTPA injected effectually without outflow was held in the tumor tissue for 24 hours, which was different from the case of gadopentetate solution injection (only 1.2%). Gd-nanoCPs highly incorporating Gd-DTPA were successfully prepared by the emulsion-droplet coalescence technique. Their releasing properties and their ability for long-term retention of Gd-DTPA in the tumor indicated that Gd-nanoCPs might be useful as an i.t. injectable device for Gd-NCT.

Preparation of lecithin microcapsules by a dilution method using the Wurster process for intraarterial administration in gadolinium neutron capture therapy.

Lecithin microcapsules containing gadolinium (Gd) were designed and prepared as a dosage form for intraarterial administration to accumulate Gd in tumors in neutron capture therapy. The microcapsules were composed of 1) a lactose core, 2) a layer of distearylamide of gadopentetic acid (Gd-DTPA-SAm) and polyvinylpyrrolidone (PVP) with or without soybean lecithin (SL) and 3) a membrane containing SL, cholesterol, stearic acid and PVP at three different compositions. A dilution method using the Wurster process was developed for small-scale preparation. In spite of using only 2 g of Gd-DTPA-SAm each, three types of microcapsules were obtained with a content of 24.9% as Gd-DTPA-SAm (3.66% as Gd) even at 150% coating level. The swelling type of microcapsules (MC-D1) did not release Gd at all for the entire 120 min of the experiment in a 0.9% saline solution. On the other hand, the rapid-erosion type (MC-D2) and the vesicle-dispersing type (MC-D3) released Gd with a lag time. The percent released depended on the coating level and the SL content in the Gd-fixing layer. A large number of droplet-like particles spouted out, and/or tubular vesicles formed with MC-D2 and MC-D3 in the saline solution. These phenomena implied that the water-insoluble Gd-DTPA-SAm would be entrapped in these particles/vesicles. When MC-D2 and MC-D3 were administered to normal rats via the hepatic artery, a Gd-accumulation as high as 70 and 71% of the injected dose was detected in the whole liver 2 h after administration. In addition, biochemical and histological evaluation of the liver after administration indicated that embolization of the microcapsules actually occurred in the blood vessels, and that necrosis induced by ischemia was not serious. These results suggested that administration of these microcapsules might be multiply repeated in order to accumulate the required amount of Gd in tumors.

Preparation of gadopentetic acid-loaded chitosan microparticles for gadolinium neutron-capture therapy of cancer by a novel emulsion-droplet coalescence technique.

Biodegradable gadopentetic acid (Gd-DTPA)-loaded chitosan microparticles (Gd-microCPs) were prepared as a device for gadolinium neutron-capture therapy (Gd-NCT) by a novel emulsion-droplet coalescence technique: a water-in-oil (w/o) emulsion A containing chitosan and Gd-DTPA in droplets and a w/o emulsion B containing NaOH in droplets were mixed and stirred to solidify chitosan as a result of collision and coalescence between droplets of each emulsion. Gd-microCPs prepared by using 100% deacetylated chitosan in 25% Gd-DTPA solution were 4.1 microns (non-lyophilized) and 3.3 microns (lyophilized) in mass median diameter, and were 3.4% in gadolinium content, corresponding to 11.7% as Gd-DTPA. The particle size and gadolinium content of Gd-microCPs were not affected by Gd-DTPA concentration in the chitosan medium. However, the deacetylation degree of chitosan influenced the particle size; as the deacetylation degree of chitosan decreased, the particle size increased. The incorporated Gd-DTPA was not released entirely from Gd-microCPs in an isotonic phosphate buffered saline solution despite the high water-solubility of Gd-DTPA (less than 0.8% with every type of Gd-microCPs). These results indicated that ion-complex formation might be contributable to incorporation of Gd-DTPA. As a preliminary study, it was confirmed that the loss of gamma-ray emission by gadolinium-loading in microparticle was negligible in the thermal neutron irradiation test in vitro. These results suggested that Gd-microCPs could be a useful device for intratumoral injection into solid tumor on Gd-NCT.

Dissolution properties of gadolinium-containing lecithin microcapsules prepared by a spouted bed process assisted with a draft

Gadolinium (Gd)-containing lecithin microcapsules were composed of a lactose core (75-90 μm) coated with polyvinylpyrrolidone (PVP), a drug layer of Gd compound and PVP, and a membrane consisting of soybean lecithin, cholesterol, stearic acid and PVP. As Gd compounds, gadopentetate dimeglumin (Gd-DTPA-DM, MC-1), gadopentetic acid (Gd-DTPA, MC-2) and a stearylamide derivative of Gd-DTPA (Gd-DTPA-SAm, MC-3) were used. The microcapsules were prepared with a high coating efficiency and a narrow size distribution, 149-177 μm. The release Gd-DTPA-DM and Gd-DTPA from MC-1 and MC-2, respectively, in a 0.9% saline solution was similar in spite of their difference in water solubility; it was delayed with a short lag time of about 10 min, followed by a rapid release and finally sustained; on the other hand, the release was remarkedly delayed and prolonged without the initial rapid release in the dextran solution. The release of water-insoluble Gd-DTPA-SAm was almost completely suppressed until 120 min in both aqueous solutions (MC-3). In the saline solution, all types of Gd-containing microcapsules were bursting devices at the initial stage, accompanying the delayed but high particle swelling, and thereafter diffusion-controlled drug-release devices. In the viscous dextran solution, they remained diffusion-controlled drug-release devices due to poor water uptake and poor swelling. These results suggested the possibility for using Gd-containing lecithin microcapsules in Gd neutron-capture therapy.

Anthropogenic origin of positive gadolinium anomalies in river waters

Positive Gd anomalies in shale-normalised rare earth element (REE SN) patterns of natural waters may provide information on the types of ligands which control surface complexation of REE on particle surfaces. However, REE SN patterns of rivers which drain densely populated and industrialised areas in Central Europe and North America are characterised by pronounced positive Gd SN anomalies, whereas rivers in thinly populated, non-industrialised areas in Värmland and Dalarna, central Sweden, and Hokkaido, Japan, do not show such anomalies. Acidification experiments suggest that, unlike the other REE, the excess Gd found in German rivers is almost completely related to the ‘dissolved’ REE fraction (< 0.2 μm) in a water sample and not to the acid-soluble particulate fraction, suggesting a negligible particle reactivity of the excess Gd. The positive Gd SN anomalies are of anthropogenic origin and are most likely to result from the application of gadopentetic acid, Gd(DTPA) 2−, in magnetic resonance imaging (MRI). In MRI, gadopentetic acid, which is an organic aqueous Gd(III) complex with very high stability constant, is used as a paramagnetic contrast agent. Since positive Gd SN anomalies in rivers, lakes, semi-closed sea basins, and coastal seas, which receive riverine REE input from industrialised, densely populated areas may (partly) be of anthropogenic origin, the positive Gd SN anomaly can no longer be used as a natural geochemical indicator.