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PubMed2002

The synthesis and radiolabeling of 2-nitroimidazole derivatives of cyclam and their preclinical evaluation as positive markers of tumor hypoxia.

UNLABELLED: The cyclam ligand (1,4,8,11-tetraazacyclotetradecane) was condensed with various azomycin-containing synthons to produce chemical compounds that could chelate radioactive metals. It was expected that these radiolabeled markers would become bound selectively to hypoxic cells on the bioreduction of their azomycin substituent. METHODS: The markers were radiolabeled with (99m)Tc, (67)Cu, or (64)Cu. Their uptake and binding to tumor cells in vitro was characterized as a function of time and oxygen concentration. These data defined the hypoxia-specific factor, the ratio of the initial rate of marker binding to severely hypoxic relative to aerobic cells. In addition, the concentration of oxygen (in the equilibrium gas phase) that inhibited binding to 50% of the maximum rate was determined. The in vivo biodistribution and clearance kinetics of the favorable markers were investigated with severe combined immune deficiency mice bearing EMT-6 tumors whose radiobiologic hypoxic fraction (RHF) was approximately 40%. The specific activity (percentage injected dose per gram [%ID/g]) in normal and tumor tissue and the tumor-to-blood and tumor-to-muscle ratios of the optimal markers were also measured for Dunning prostate carcinomas of anaplastic (RHF = 15%-20%) and well-differentiated (RHF < 1%) histology growing in Fischer X Copenhagen rats. Planar images were acquired with some markers from these tumor-bearing rats. RESULTS: The tumor uptake of these cyclam-based markers is approximately 10 times higher when they are labeled with copper isotopes than when labeled with (99m)Tc. FC-327 and FC-334, di-azomycin-substituted cyclams, exhibited hypoxia-specific factors > or = 7.0. The oxygen concentration that inhibited their binding to 50% of the maximal rate was approximately 0.5% O(2), similar to that of the radiobiologic oxygen effect. The %ID/g of (64)Cu-FC-334 retained in EMT-6 tumors in mice and in the anaplastic and well-differentiated prostate tumors in rats 6 h after administration was approximately 6.5, 0.4, and 0.1, respectively. Marker activity in tumor was always less than that in liver and kidney. The tumor-to-blood and tumor-to-muscle ratios of (64)Cu-FC-327 and (64)Cu-FC-334 activity in R3327-AT tumor-bearing rats are higher than those observed for (64)Cu-di-acetyl-bis (N(4)-methylthiosemicarbazone) and approach those of beta-D-(125)I-iodinated azomycin galactopyranoside, the optimal hypoxia marker of the azomycin-nucleoside class. CONCLUSION: These data suggest that some azomycin-cyclams exhibit good hypoxia-marking potential to tumor cells in vitro and to animal tumors of known RHF. Both PET and SPECT could be used to image tumor hypoxia with markers labeled with (64)Cu and (67)Cu, respectively.

Animals↗
PubMed1977

Radioactive labeling of protein carboxyl groups on factor VIII: use of carbodiimides for nuclear medicine.

Carbodiimides have been used to study macromolecular structure and to produce immunologically active antigens. We have used this method to label a labile coagulation protein, factor VIII, with 14C-glycine-ethyl-ester. No discernible chemical change, loss of biologic function in vitro, or alteration of the plasma disappearance of factor VIII resulted. The carbodiimide labeling method has potentially broad application because many biologic molecules contain carboxyl groups that are generally not critical to their chemical or immunologic character. This method can be used to incorporate short-lived positron emitters, such as 11C and 13N, into biologic compounds, or to attach ligands to useful antibodies for subsequent chelation to radioactive metals, such as 111In. Carbodiimides are especially useful for radionuclidic labeling of labile proteins because of the mild conditions, rapid reaction, and firmly attached label.

Carbodiimides↗
PubMed1998

Radioactive materials in recycled metals--an update.

In April 1995, Health Physics published a review paper titled "Radioactive Materials in Recycled Metals." At that time, 35 accidental meltings of radioactive sources in metal mills were reported, including 22 in the U.S., along with 293 other events in the U.S. where radioactive material was found in metals for recycling. Since that date, there have been additional accidental meltings of radioactive sources in metal mills both in the U.S. and elsewhere. There also was an incident in Texas that involved stolen radioactive devices, which resulted in exposures of members of the general public. Also, the U.S. Nuclear Regulatory Commission took steps to address the underlying problem of inadequate control and accountability of radioactive materials licensed by the Nuclear Regulatory Commission. The Steel Manufacturers Association made available data collected by its members beginning in 1994 that expanded the database for radioactive materials found by the metal recycling industry in recycled metal scrap to over 2,300 reports as of 30 June 1997.

Conservation of Natural Resources↗
PubMed2002

Radioactivity and heavy metal composition of Nigerian phosphate rocks: possible environmental implications.

Phosphate rock samples collected from the Dange Formation within the Sokoto basin were analyzed for trace element constituents using instrumental neutron activation analysis (INAA) and X-ray fluorescence analysis (XRFA) techniques, while natural activity concentrations due to 235U, 232Th, and 40K were determined by gamma-ray spectrometry. The analytical results show that the average concentrations of some toxic elements (As, Sb, Cr, and Zn) in phosphate rocks are not appreciably different from that in agricultural soils. However the U and Th contents are enriched significantly in comparison. The results were used to assess the environmental toxicity of heavy metals and radiation hazard attributable to the direct application of phosphate rock as fertilizer.

Agriculture↗
PubMed2000

Engineering Deinococcus radiodurans for metal remediation in radioactive mixed waste environments.

We have developed a radiation resistant bacterium for the treatment of mixed radioactive wastes containing ionic mercury. The high cost of remediating radioactive waste sites from nuclear weapons production has stimulated the development of bioremediation strategies using Deinococcus radiodurans, the most radiation resistant organism known. As a frequent constituent of these sites is the highly toxic ionic mercury (Hg) (II), we have generated several D. radiodurans strains expressing the cloned Hg (II) resistance gene (merA) from Escherichia coli strain BL308. We designed four different expression vectors for this purpose, and compared the relative advantages of each. The strains were shown to grow in the presence of both radiation and ionic mercury at concentrations well above those found in radioactive waste sites, and to effectively reduce Hg (II) to the less toxic volatile elemental mercury. We also demonstrated that different gene clusters could be used to engineer D. radiodurans for treatment of mixed radioactive wastes by developing a strain to detoxify both mercury and toluene. These expression systems could provide models to guide future D. radiodurans engineering efforts aimed at integrating several remediation functions into a single host.

Bacterial Proteins↗
PubMed1987

The effect of lipophilic substituents on the biological properties of EDTA complexes containing paramagnetic metal ions.

Complexes of the radioactive paramagnetic metal ions 51Cr(III), 54Mn(II), 59Fe(III), 57Co(II), 64Cu(II) and 153Gd(III) were prepared with EDTA and its derivative containing the lipophilic 1-(4-methylphenyl)-group (MPEDTA), together with the corresponding 99mTc-compounds. The formation of these complexes was verified by electrophoresis and they were screened for potential use as MRI hepatobiliary contrast agents by biodistribution studies in mice. In this series, the MPEDTA complexes of 54Mn(II) and 64Cu(II) showed increased urinary excretion compared to the unsubstituted EDTA complexes, while the MPEDTA complexes of 99mTc, 59Fe, 57Co, 153Gd and particularly 51Cr demonstrated improved hepatobiliary excretion. Further lipophilic substitution should enhance this property but the preparation of such ligands is complicated by cyclisation reactions.

Animals↗
PubMed2005

In situ gamma spectrometry measurements and Monte Carlo computations for the detection of radioactive sources in scrap metal.

A very limited number of field experiments have been performed to assess the relative radiation detection sensitivities of commercially available equipment used to detect radioactive sources in recycled metal scrap. Such experiments require the cooperation and commitment of considerable resources on the part of vendors of the radiation detection systems and the cooperation of a steel mill or scrap processing facility. The results will unavoidably be specific to the equipment tested at the time, the characteristics of the scrap metal involved in the tests, and to the specific configurations of the scrap containers. Given these limitations, the use of computer simulation for this purpose would be a desirable alternative. With this in mind, this study sought to determine whether Monte Carlo simulation of photon flux energy distributions resulting from a radiation source in metal scrap would be realistic. In the present work, experimental and simulated photon flux energy distributions in the outer part of a truck due to the presence of embedded radioactive sources in the scrap metal load are compared. The experimental photon fluxes are deduced by in situ gamma spectrometry measurements with portable Ge detector and the calculated ones by Monte Carlo simulations with the MCNP code. The good agreement between simulated and measured photon flux energy distributions indicate that the results obtained by the Monte Carlo simulations are realistic.

Computer Simulation↗
PubMedDate not supplied

[Effect of combined radioactive and chemical (heavy metals, herbicides) pollution on the yield of cytogenetic disruptions in the intercalary meristem of spring barley].

The yield of aberrant cells and their loading with lesions of intercalary meristem of spring barley in conditions of the combined action of 137Cs, heavy metals and 2.4-D herbicide was studied. At simultaneous insertion of 137Cs and Cd into the soil, the type of non-linearity of the yield of aberrant cells was determined by radioactive pollution: in a range of low concentrations the synergistic effects took place, in a range of higher ones the antagonistic effects did. In the presence of cadmium, the severity of radiation induced damage to aberrant cells was significantly less. The interaction in 137Cs-Pb pair had an antagonistic character. The yield of aberrant cells was determined mainly by lead, whereas the radioactive pollution played the main role in loading of the aberrant cells with lesions. At the combined pollution with 137Cs and other contaminants, the antagonistic effects were more pronounced with Pb than with Cd, and further increased with the herbicide, both in the test on frequency of aberrant cells and the test on the loading of aberrant cells with lesions. In case of combination of the chemical agents the non-linear effects in test on loading of aberrant cells with lesions were mainly synergistic, whereas in the test on frequency of aberrant cells they were antagonistic. Only Pb-Cd pair and only in the test on loading of aberrant cells with lesions no significant non-linear effects were found. The results show high rate of the induction of synergistic and antagonistic effects in conditions of the combined action of low concentrations of the investigated agents on plants. These effects substantially determined the yield of cytogenetic disturbances in the studied range.

2,4-Dichlorophenoxyacetic Acid↗
PubMed2006

Scrap metals industry perspective on radioactive materials.

With more than 80 reported/confirmed accidental melts worldwide since 1983 and still counting, potential contamination by radioactive materials remains as a major concern among recycled scrap and steel companies. Some of these events were catastrophic and have cost the industry millions of dollars in business and, at the same time, resulted in declining consumer confidence. It is also known that more events with confirmed radioactive contamination have occurred that involve mining of old steel slag and skull dumps. Consequently, the steel industry has since undergone massive changes that incurred unprecedented expenses through the installation of radiation monitoring systems in hopes of preventing another accidental melt. Despite such extraordinary efforts, accidental melts continue to occur and plague the industry. One recent reported/confirmed event occurred in the Republic of China in 2004, causing the usual lengthy shutdown for expensive decontamination efforts before the steel mill could resume operations. With this perspective in mind, the metal industry has a long-standing opposition to the release of radioactive materials of any kind to commerce for fear of contamination and the potential consequences.

Decision Making↗