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PubMed1981

[Metalloporphyrin study in experimental carcinology (author's transl)].

Antitumoral effects and intratumoral concentrations of a metalloporphyrin were studied in mice with solid chemo-induced or transplanted tumors. The synthesis of this molecule was realised both with a stable metal (TPPS4SnCl2) (TPPS4InCl) and a radioactive metal (TPPS4(113)SnCl2) (TPPS4(111)InCl). The metal is introduced into the tetrapyrollic structure to give this molecule very high stability. The effect of the stable metalloporphyrin on tumoral kinetic parameters was analyzed. No tumoral regression was observed during the various experimental procedures. Even though radioactive molecules were found in the tumours, they were also present as high concentrations in the liver, spleen and kidneys, more than 72 hours after injection. Results are compared with those of various authors who used a molecule without metal, levels being measured by fluorescence in various organs and in the tumors. The interest of this metalled molecule in carcinology is discussed in relation to these new results.

Animals↗

PubMed2004

Characteristics of dioxins and metals emission from radwaste plasma arc melter system.

This study investigated the emission characteristics of PCDD/Fs and the partitioning of three heavy metals (Cd, Hg and Pb) and two radioactive metal surrogates (Co and Cs) in a radwaste plasma arc melter system. Typical mixtures of low-level radioactive wastes were simulated as the trial burn surrogate wastes. The emission of PCDD/Fs and the partitioning of the metals were strongly influenced by the feed waste stream and melter operating temperature, respectively. The emissions of PCDD/Fs, cadmium and lead were greatly enhanced when the polyvinyl chloride was included in the feed waste stream. Most of the nonvolatile cobalt partitioned into the glass. A significant quantity of cesium, cadmium and lead was vaporized during the highest melter temperature test. A lower melter temperature resulted in more cesium, cadmium and lead species remaining in the glass. The results of this study suggest that wet scrubbing as well as a low-temperature two-step fine filtration, or both of them together could not effectively capture the gas-phase or fine particle phase PCDD/Fs and mercury species. In order to effectively treat low-level radioactive waste streams, the tested high-temperature melter should include an adsorption system, which could collect the gas-phase PCDD/Fs and mercury species.

Adsorption↗

PubMedDate not supplied

Terminal-modified polylysine-based chelating polymers: highly efficient coupling to antibody with minimal loss in immunoreactivity.

A method is suggested for the preparation of chelating polymers containing a single terminal reactive group capable of interaction with proteins. These polymers were synthesized from N-CBZ-polylysine and DTPA and contain a terminal SH or pyridyldisulfide group. A polymer molecule with MW 13,500 is able to carry up to 40 DTPA residues. Polymers easily and quantitatively bind with antibodies (Fab fragments of antimyosin antibodies R11D10) with minimal effect on antibody immunoreactivity as revealed in ELISA assay and in direct immunoanalysis. Conjugates prepared can chelate radioactive metal ions reaching very high specific radioactivity (greater than 1 mCi 111In/10 micrograms of protein). Perspectives for their application are discussed.

Antibodies↗

PubMed1983

Interactions between selenium and mercury in mice: marked retention in the lung after inhalation of metallic mercury.

The distribution of 203Hg after inhalation of radioactive metallic mercury (4.3 mumol 203Hg0/kg body wt. for 1 h) was studied in saline (control) and selenite (10 mumol/kg body wt. intraperitoneally, i.p.) pretreated male C57BL mice by means of whole-body autoradiography and scintillation counting. Selenite pretreatment did not apparently change the immediate uptake and distribution of 203Hg (presumably inorganic Hg after oxidation in the different organs) but markedly increased the retention time in the whole body. The most marked retention was seen in the lungs where the selenite-pretreated animals had 200 times higher concentration as compared to control animals 14 days after inhalation. In other organs the corresponding value ranged between 1 (brain) and 12 (spleen). Selenite-pretreated and control animals showed the same low rate of exhalation of 203Hg after the inhalation period, while the latter animals eliminated significantly more through the urine and faeces (measured only during the first 24 h). When inversely radioactive selenite (75Se-selenite) was injected i.v. into animals 1 h earlier exposed to non-radioactive Hg0 (by inhalation), the lung concentration of 75Se after 24 h was 4 times higher than that of control animals. When radioactive mercury was injected i.v. in the form of 203HgCl2 (4.3 mumol/kg body wt.), selenite (10 mumol/kg body wt., i.p.) increased the retention time in the body, more so than after 203Hg0 inhalation. In this case the mercury was retained especially in the serum, red pulp of the spleen and liver (reticulo-endothelial system). 75Se-selenite injected i.v. after i.p. administration of non-radioactive HgCl2 in the same doses as above similarly accumulated more in serum, spleen and liver as compared to control animals. It is presumed that while injected selenite and inorganic mercury (Hg2+) interact strongly in the serum, increasing each other's uptake and retention especially in the reticulo-endothelial system, inorganic mercury retained in various organs after oxidation of Hg0 upon inhalation interacts with selenium mainly intracellularly. This occurs especially in the lungs, where initially high concentrations of mercury are found after inhalation.

Animals↗

PubMed2004

Behavior of toxic metals and radionuclides during molten salt oxidation of chlorinated plastics.

Molten salt oxidation is one of the promising alternatives to incineration for chlorinated organics without the emission of chlorinated organic pollutants. This study investigated the behavior of three hazardous metals (Cd, Pb, and Cr) and four radioactive metal surrogates (Cs, Ce, Gd, and Sm) in the molten Na2CO3 oxidation reactor during the destruction of PVC plastics. In the tested temperature ranges (1143 1223K) and NaCl content (0-10%), the impact of temperature on the retention of cadmium and lead in the molten salt reactor was very small, but that of the NaCl content for their retention was relatively higher. The influence of NaCl accumulation was, however, proven to be practically negligible due to the low-temperature operating characteristics of the molten salt oxidation system. Neither temperature increase nor chlorine accumulation in the MSO reactor reduced the retention of Cr, Ce, Gd, and Sm. Over 99.98% of these metals remained in the reactor. The influence of the temperature on the cesium behavior is relatively large for a chlorine addition, however, over 99.7% of cesium remained in the reactor throughout the entire test. The experimental metal entrainment rate and the entrained metal particle size distribution agree well with the theoretical equilibrium metal distributions.

Chlorine Compounds↗

PubMed1986

The in vivo cross-linking of proteins and DNA by heavy metals.

Cross-linking of proteins to DNA in live, intact Novikoff ascites hepatoma cells exposed in vitro to different concentrations of CuSO4, Pb(NO3)2, HgCl2, and AlCl3 was studied. Protein-DNA complexes were separated by high-speed centrifugation of cells solubilized in buffered 4% sodium dodecyl sulfate and assayed by electrophoretic separation of proteins associated with the DNA-containing pellets. Concentration dependence experiments showed that the optimal cross-linking occurred at metal concentration of 0.5 mM for CuSO4, HgCl2, and AlCl3 while the optimal cross-linking for Pb(NO3)2 was at 5 mM. For some metals at concentrations higher than optimal, the amounts of cross-linked proteins decreased significantly. Immunochemical analysis of the cross-linked proteins using antibodies to matrix, chromatin, lamins, and cytokeratin fractions demonstrated that some, but not all, members of these protein families became cross-linked to the DNA. Each metal exhibited a cross-linking pattern of its own, different from those of the other metals. Radioactive labeling experiments showed that all the metals tested became associated with the DNA-protein pellets within 1 h after their addition to the incubation medium. However, hexavalent chromium required more than 2 h before appearing in the DNA-protein pellets in significant amounts.

Aluminum↗

PubMed1990

Uptake of metallic mercury and mercuric ion by human erythrocytes.

Uptake of metallic mercury (Hg degrees) and mercuric ion (Hg2+) by erythrocytes was studied by incubating erythrocytes with various concentrations of radioactive metallic mercury and mercuric ion in phosphate-buffered saline (pH 6.8) or plasma at 25 degrees C for 30 min. Radioactivity taken up in the cytosol (endsome) and stroma were determined with a gamma scintillation counter. The radioactivity ratio of the mercury recovered in the cytosol fraction to metallic mercury incubated in the saline was significantly higher than the ratio of that to mercuric ion. Similar findings were observed in erythrocytes incubated with metallic mercury and mercuric ion in plasma, although the recovered radioactivity of mercury in the cytosol of erythrocytes incubated with metallic mercury or mercuric ion in plasma was less than that incubated in phosphate-buffered saline. Thus, erythrocytes incubated with metallic mercury took up a larger amount of mercury than those incubated with mercuric ion. Discussion is made on these findings.

Catalase↗

PubMed2002

Self-expandable covered metallic esophageal stent impregnated with beta-emitting radionuclide: an experimental study in canine esophagus.

PURPOSE: A specially designed self-expandable covered metallic stent impregnated with the beta-emitting radioisotope 166Ho (166Ho, energy: 1.85 and 1.76 MeV, T12: 26.8 h) was developed at our institute for the purpose of intraluminal palliative brachytherapy, as well as for treating malignant esophageal stricture and swallowing difficulty. The aim of this study was to evaluate the tissue response to brachytherapy and the safety of the radioactive metallic stent with regard to the normal canine esophagus before clinical application. METHODS AND MATERIALS: 166Ho was impregnated into the polyurethane membrane (50 micron thickness) covering the outer surface of a self-expandable metallic stent (diameter, 18 mm; length, 40 mm). Stents with radioactivity 4.0-7.8 mCi (Group A, n = 15), 1.0-1.8 mCi (Group B, n = 5), and 0.5-0.7 mCi (Group C, n = 5) were placed in the esophagi of 25 healthy beagle dogs, and the stents were tightly anchored surgically to prevent migration. The estimated radiation dose calculated by Monte Carlo simulation was 194-383 Gy in Group A, 48-90 Gy in Group B, and 23-32 Gy in Group C. The dogs were killed 8-12 weeks after insertion of the stents, and histologic examinations of the esophageal walls were performed. RESULTS: In Group A, 3 of 15 dogs died of wound infection, so specimens were obtained from only 12 dogs; all 12 cases showed esophageal stricture with mucosal ulceration. Microscopically, severe fibrosis and degeneration of the muscular propria were found in 3 dogs, complete fibrosis of the entire esophageal wall was found in 7 dogs, and esophageal fibrosis with radiation damage within periesophageal soft tissue was found in 2 dogs. However, esophageal perforation did not develop, despite extremely high radiation doses. In Group B, glandular atrophy and submucosal fibrosis were found, but the muscular layer was intact. In Group C, no histologic change was found in 3 dogs, but submucosal inflammation and glandular atrophy with intact mucosa were found in 2 dogs. CONCLUSIONS: A radioactive, self-expandable covered metallic stent can be used as an alternative therapeutic modality for the palliative treatment of malignant esophageal stricture.

Animals↗

PubMed1984

Organ and cellular distribution of inhaled metallic mercury in the rat and Marmoset monkey (Callithrix jacchus): influence of ethyl alcohol pretreatment.

Distribution of inhaled radioactive metallic mercury vapour (203Hg0) in rats and Marmoset monkeys (Callithrix jacchus), with or without pretreatment by ethyl alcohol or aminotriazole (rat), was studied by means of whole-body autoradiography, microautoradiography and scintillation counting of excised organs. Metallic mercury is oxidized by the catalase-H2O2 complex (Complex I) to the ionic form (Hg2+) and is known to be accumulated and retained in organs such as lungs, liver, myocardium, and brain, apparently after local oxidation in these organs. To this list of organs can be added the whole respiratory tract (nasal mucosa, trachea, and bronchi), a number of endocrine organs such as adrenal cortex, thyroid, corpora lutea of the ovaries, and interstitial tissues of the testes, the uvea and retina of the eye, and the salivary glands. In the liver, a regionalized pattern of distribution corresponding to the periportal hepatocytes was observed. Similarly, the subcapsular parts of the adrenal cortex (mainly the zona glomerulosa) were responsible for most of the adrenal mercury oxidation and retention. These organs (liver, adrenal) thus have a reserve capacity to oxidize Hg0. This is apparent also by the fact that ethyl alcohol and aminotriazole (known catalase inhibitors)--which depress oxidation and retention in most organs and whole body and thus increase blood concentrations of Hg0--cause an increased retention in most liver and adrenal cells.

Amitrole↗

PubMed2003

Genome of Geobacter sulfurreducens: metal reduction in subsurface environments.

The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity.

Acetates↗

PubMedDate not supplied

Progestin-rhenium complexes: metal-labeled steroids with high receptor binding affinity, potential receptor-directed agents for diagnostic imaging or therapy.

In order to investigate the possibility of developing diagnostic imaging agents for steroid-positive tumors that are labeled with the readily available radionuclide technetium-99m, we prepared four conjugate systems in which a progestin is linked to a metal chelate system. Three of these are bis-amino bis-thiol (BAT or N2S2) systems and are linked through carbon-21 of progesterone or the 17 alpha- or 11 beta-position of a nortestosterone type progestin. The fourth, an amino-amido-thiol-alcohol chelate (N2OS) system, is linked at the 16 alpha,17 alpha-positions of a dihydroprogesterone. As a model for technetium-labeled complexes, all four chelate systems were converted to their oxo-rhenium complexes. Of the four possible diastereomers in the 16 alpha,17 alpha-system, only one was isolated, while of the four possible diastereomers in the other systems, a syn pair and an anti pair (linker methylene vs rhenium-oxo, relative to the N2S2 plane) were separated in the 17 alpha-substituted series, a syn pair was isolated in the 21-substituted series, and a syn pair and the two individual anti diastereomers were separated in the 11 beta-substituted series. In competitive radiometric receptor binding assays, the 21-, 17 alpha-, and 16 alpha,17 alpha-linked systems had low affinity for the progesterone receptor (less than 0.3% that of promegestone (R5020) or 2% that of progesterone). By contrast, the two anti diastereomers of the 11 beta-linked system had affinities that were 10% and 44% that of R5020 (or 64% and 283% that of progesterone) and the syn pair had an affinity 25% that of R5020 (or 161% that of progesterone). The latter finding indicates that it is possible to prepare metal-labeled steroids that retain high affinity for steroid receptors. These and related systems, when complexed with radioactive metals, may be useful in vivo as receptor-directed agents for diagnostic imaging or therapy of steroid receptor-positive tumors.

20-alpha-Dihydroprogesterone↗

PubMed2003

Subcritical (hot/liquid) water dechlorination of PCBs (Aroclor 1254) with metal additives and in waste paint.

No disposal option exists for "mixed wastes" such as paint scrapings that are co-contaminated with polychlorinated biphenyls (PCBs) and radioactive metals. Either removal or destruction of the PCBs is required prior to disposal. Comparison of subcritical water dechlorination (350 degrees C, 1 h) of Aroclor 1254 in paint scrapings (180 ppm) and of standard Aroclor 1254 showed significantly enhanced dechlorination in the presence of paint. While no significant degradation was observed for standard Aroclor (no paint), the dechlorination of PCBs in paint was 99, 99, and 80% for the hepta-, hexa-, and pentachlorinated congeners, respectively, indicating that metals in the paint enhanced the dechlorination reactions. Adding metals to the standard Aroclor (no paint) reactions enhanced PCB dechlorination in subcritical water in descending order of activity: Pb approximately = Cu > Al > Zn > Fe. In the presence of both zerovalent and divalent lead and zerovalent copper in subcritical water (350 degrees C, 1 h), 99% of the Aroclor 1254 mixture (tetra- to heptachlorinated biphenyls) was dechlorinated. High dechlorination (ca. 95%) was also achieved with zerovalent aluminum. In contrast to other metals, lead retained its degradation ability at a lower temperature of 250 degrees C after 18 h. The high degradation efficiency achieved using metal additives in water at reasonable temperatures and pressures demonstrates the potential for subcritical water dechlorination of PCBs in paint scrapings and, potentially, in other solid and liquid wastes.

Chlorodiphenyl (54% Chlorine)↗

PubMed2006

Risk assessment for chemical pickling of metals contaminated by radioactive materials.

In recent years, many cases of contamination of metal scraps by unwanted radioactive materials have occurred. Moreover, international organisations are evaluating the possibility to re-use or to recycle metals coming from nuclear power plants. The metal recycling industry has started to worry about radiation exposure of workers that could be in contact with contaminated metals during each manufacturing phase. Risks are strongly dependent on the radiation source features. The aim of this study is to perform risk assessment for workers involved in chemical pickling of steel coils. Monte Carlo simulations have been performed, using the MCNP package and considering coils contaminated with (60)Co, (137)Cs, (241)Am and (226)Ra. Under the most conservative conditions (coil contaminated with 1.0 kBq g(-1) of (60)Co), the dose assessment results lower than the European dose limit for the population (1 mSv y(-1)), considering a maximum number of 10 contaminated coils handled per year. The only exception concerns the case of (241)Am, for which internal contamination could be non- negligible and should be verified in the specific cases. In every case, radiation exposure risk for people standing at 50 m from the coil is widely <1 mSv y(-1).

Body Burden↗

PubMed1991

Exhalation of metallic mercury by acatalasemic, hypocatalasemic and normal mice exposed to metallic mercury vapor.

In order to elucidate the amounts of metallic mercury exhaled from mice having different amounts of catalase activity, normal, homozygous hypocatalasemic and acatalasemic mice were exposed to radioactive metallic mercury vapor at three levels of concentrations (0.072, 0.144, and 0.297 mg/m3). The timed and cumulative amounts of metallic mercury exhaled from the mice were used to classify them, in the descending order, as being acatalasemic, hypocatalasemic, and normal at the three environmental mercury concentrations. The statistical differences in the mean values among the acatalasemic, hypocatalasemic, and normal mice were calculated by the use of one-way ANOVA and multiple comparison of the mean values by Tukey's method. The mean values of the timed amounts of exhaled metallic mercury were found to be significantly different (P less than 0.05) among the three kinds of mice several hours after exposure, and those of the cumulative amounts of exhaled metallic mercury were in the descending order of acatalasemic, hypocatalasemic and normal mice, and were significantly different among the three types of mice almost over the entire time course. Thus, negative correlation coefficients were obtained between the logarithms of the catalase activity in the lungs and the blood, and the logarithms of the cumulative amounts of exhaled metallic mercury.

Acatalasia↗

PubMed1983

Intracellular sites of toxic metals.

In summary, this brief overview of the cellular localization of toxic metals in renal tubular cells demonstrates a spectrum of mechanisms for the sequestration of the metals. Common features are affinity for a metal-binding protein, such as insoluble acidic nuclear proteins or the soluble, low-molecular weight metallothionein. Accumulation in lysosomes follows assimilation of metal containing protein by lysosomes or autophagocytosis of degenerating metal containing mitochondria. Currently available methods have not demonstrated the presence of metals in immune complex deposits in glomerular basement membrane and epithelial cells. The principal methods employed for the localization of metals within cells have been X-ray microanalysis of thin preparation of tissue, or direct analysis of subcellular fractions by atomic absorption spectroscopy or detection of radioactive metal.

Cadmium↗

PubMed1996

Metal ion speciation in blood plasma: gallium-67-citrate and MRI contrast agents.

UNLABELLED: Metal chelate ions are commonly used in medical diagnostic imaging as MRI contrast or imaging agents. The efficacy of these metals depends on their in vivo behavior, which in turn depends on their in vivo speciation. METHODS: A computer model has been used to simulate the speciation of Ga3+ and Gd3+ in blood plasma. The model has been tested against known clinical data and then used to investigate Ga3+ uptake by tumor cells. The iatrogenic effect of a gadopentetic acid enhanced MRI scan upon the biodistribution of 67Ga citrate has also been calculated. RESULTS: The speciation of Ga3+ calculated using the computer model is concordant with clinical data. The results support transferrin mediated uptake of Ga3+ by tumor cells but also account for Ga(III) biodistribution observed in hypotransferrinemic subjects. In a study of the effect of gadopentetic acid upon 67Ga gallium citrate, neither residual DTPA nor [Gd(DTPA)]2- cause significant changes in the speciation of Ga(III). The calculations show that dissociation of 4% of the administered gadopentetic acid results in the formation of a mixed, Gd(III) and Ga(III), metal transferrin complex and a 100-fold increase in the concentration of [Ga(OH)4]-. CONCLUSION: Computer simulation is a valuable tool which can be used to explain/understand in vivo behavior of radioactive metal ions.

Citrates↗

PubMed2005

Effects of a holmium-166 incorporated covered stent placement in normal canine common bile ducts.

PURPOSE: A specially designed self-expandable covered metallic stent incorporated with beta-emitting radioisotope, Holmium-166 (Ho-166), was developed for delivering intraluminal brachytherapy as well as for internal bile drainage in malignant biliary stricture. The purpose of the study was to demonstrate the safety and tissue response of the radioactive metallic stent on the normal canine common bile duct (CBD) prior to the clinical application. MATERIALS AND METHODS: Nitinol self-expandable stents (diameter; 4 mm, length; 20 mm) were covered with polyurethane membrane (50 microm thick) containing 21 to 135 muCi of Ho-166 (mean, 77.9 microCi). To prevent migration of stent, the membrane covered only the middle 1 cm of the stent and the ends of the stent were left uncovered. The stents were placed in the CBD of 20 healthy beagle dogs. For control, non-radioactive covered stents were placed in another three dogs. The dogs were killed 3 to 6 months after stent insertion and histopathologic examination of CBD was performed. RESULTS: There was no stent migration in all cases. Varying degrees of papillary mucosal hyperplasia leading to significant narrowing of the lumen was observed within the lumen of the bare portion and under the mucosal surface of the non-radioactive covered stents. However, fibrosis was noted in Ho-166 coated area, instead of mucosal hyperplasia. Severity of fibrosis was correlated with estimated radiation dose. Despite high dose, there was no perforation of CBD wall. The membrane of Ho-166 coat was disrupted in some cases of 6 months follow-up. CONCLUSIONS: Holmium-166 incorporated covered stents demonstrated fibrosis of CBD wall and inhibition of ingrowth of mucosal hyperplasia without serious complication such as perforation, while control group showed severe mucosal hyperplasia.

Alloys↗

PubMed1989

A novel derivative of the chelon desferrioxamine for site-specific conjugation to antibodies.

We describe the preparation of the modified chelator aminooxyacetyl-ferrioxamine, and the replacement of its iron atom by 67Ga at high specific activity. The aminooxy function of this compound was allowed to react with the aldehyde groups generated by the periodate oxidation of the oligosaccharide of a mouse IgG1 monoclonal antibody (MAb) directed against carcino-embryonic antigen (CEA). The use of the aminooxy group allowed a stable bond to be formed between the chelon and the antibody with no need for reduction. Iron was removed from the ferrioxamine moiety and replaced by 67Ga either before or after conjugation of the chelon to the antibody. In either case the labelled antibody was injected into nude mice bearing a human colon carcinoma having the appropriate antigenicity. Unoxidized antibody, labelled with 125I by conventional methods, was co-injected as an internal control. Additional control experiments were carried out with a non-immune IgG using the same 67Ga-labelled modified chelon as above. The in vivo distribution of the modified antibodies was evaluated at various times between 24 and 96 hr after injection. The methods used were gamma-camera imaging and, more quantitatively, gamma-counting of the various organs after dissection. Interestingly, with the metal-chelon-labelled antibody, the intensity and specificity of tumor labelling was comparable and in some cases superior to the results obtained with radio-iodinated antibody. In particular, there was almost no increase in liver and spleen uptake of radioactive metal relative to radio-iodine, contrary to what has been observed with most antibodies labelled with 111In after conjugation with DTPA.

Animals↗