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Radiological impact on the workers, members of the public, and environment from the partial decommissioning of Pakistan Research Reactor-I and its associated radioactive residues.

The Pakistan Research Reactor-I (PARR-I) is a swimming pool type research reactor originally designed and built for a thermal power of 5 MW using High Enriched Uranium (HEU) fuel. In 1990-1991 the reactor was redesigned, partially decommissioned and recommissioned to operate with Low Enriched Uranium (LEU) fuel at a thermal power of 10 MW. An essential requirement, construction and commissioning of a wet spent fuel storage bay and fabrication of an irradiated fuel transfer cask were completed before actual dismantling of the reactor core. During the partial decommissioning operations, radioactive waste generated included 600 m3 low-level liquid radioactive waste and 14 m3 of solid radioactive waste with an average specific activity of 4.52 Bq ml(-1) and 2.22 kBq g(-1), respectively. External radiation doses of the workers were determined using TLD (NG 6,7) and direct reading dosimeters. The maximum individual external radiation dose received by any worker during this practice was 5 mSv, which was 25% of the annual dose limit of 20 mSv. Detection and measurement of internal contamination was carried out using bioassay techniques. During the whole operation, not a single case of internal contamination was detected. The ambient radiation levels around waste seepage pits are periodically monitored using TLD (G-2 cards) and G. M. radiation survey meters. Underground migration of radioactivity is checked by analyzing seepage water samples taken from boreholes that have been dug at different locations in the vicinity of the radioactive residues. The monitoring around disposal sites containing radioactive residues has been continued during the last 9 y and will be continued in the future. So far, no rise in the environmental gamma radiation dose level and migration of underground radionuclides has been found in the vicinity of these disposal sites. Working personal during the decommissioning of PARR-I have been found to be radiologically safe. Adherence to the ALARA principle, sound decommissioning and proper radioactive waste disposal procedures helped to protect the working personnel, members of the public, and the environment from the harmful effects of the ionizing radiations present due to the partial decommissioning of the research reactor and its radioactive residues. Experience gained during this work, along with the current international procedures, will be helpful for full restoration of the environment from radioactive residues likely to be generated in the future from any other practices in Pakistan.

Body Burden↗

Measurement of specific radioactivity in proteins separated by two-dimensional gel electrophoresis.

We report a method to quantify the specific radioactivity of proteins that have been separated by 2-DE. Gels are stained with SyproRuby, and protein spots are excised. The SyproRuby dye is extracted from each spot using DMSO, and the fluorescence is quantified automatically using a plate reader. The extracted gel piece is then dissolved in hydrogen peroxide and radioactivity is quantified by liquid scintillation counting. Gentle agitation with DMSO for 24 h was found to extract all the SyproRuby dye from gel fragments. The fluorescence of the extract was linearly related to the amount of BSA loaded onto a series of 1-D gels. When rat muscle samples were run on 2-DE gels, the fluorescence extracted from 54 protein spots showed a good correlation (r = 0.79, p < 0.001) with the corresponding spot intensity measured by conventional scanning and image analysis. DMSO extraction was found not to affect the amount of radioactive protein left in the gel. When a series of BSA solutions of known specific radioactivity were run on 2-DE gels, the specific radioactivity measured by the new method showed a good correlation (r = 0.98, p < 0.01, n = 5) with the specific radioactivity measured directly before loading. Reproducibility of the method was measured in a series of 2-DE gels containing proteins from the livers of rats and mice that had been injected with [35S]methionine. Variability tended to increase when the amount of radioactivity in the protein spot was low, but for samples containing at least 10 dpm above background the CV was around 30%, which is comparable to that obtained when measuring protein expression by conventional image analysis of SyproRuby-stained 2-DE gels. Similar results were obtained whether spots were excised manually or using a spot excision robot. This method offers a high-throughput, cost-effective and reliable method of quantifying the specific radioactivity of proteins from metabolic labelling experiments carried out in vivo, so long as sufficient quantities of radioactive tracer are used.

Animals↗

Topographical assessment of accumulated radioactivity from [14C]2-deoxyglucose and [6(-14C)]glucose in rat forebrain at different survival periods.

The uptake and retention of radioactivity was measured in discrete areas of rat brain at different times after i.v. injection of [14C]2-deoxyglucose or [6(-14)C]glucose, in unrestrained rats. In most brain regions, the accumulation of radioactivity from the two compounds was similar when a 30-min survival period for [6(-14)C]glucose was compared to a 45-min survival period for [14C]2-deoxyglucose. However, at those times, autoradiographic images of the hippocampus and piriform cortex appeared distinctly different for [14C]2-deoxyglucose and [6(-14)C]glucose. Relatively more radioactivity accumulated from [14C]2-deoxyglucose, compared to [14C]glucose, in the stratum lacunosum-moleculare of the hippocampus and in layer 4 of the isocortex. In contrast, relatively more radioactivity accumulated from [6(-14)C]glucose, compared to [14C]2-deoxyglucose, in the molecular and granule cell layers of the dentate gyrus, the CA1 pyramidal cell layer of the hippocampus, and in layer 2 of the piriform cortex. When rats were killed 5 min after injection of [6(-14)C]glucose, the relative neuroanatomical distribution of radioactivity was similar to the 30-min survival period, except in layer 4 of the isocortex, where relatively more radioactivity was present at the early time. When rats were killed 5 min after injection of [14C]2-deoxyglucose, in 20 of 24 brain regions examined, the absolute and relative amounts of accumulated radioactivity were similar when compared to that of the 45-min survival period. In contrast, the absolute and relative amounts of radioactivity were significantly greater for the 5-min compared to the 45-min survival period, in the CA1 pyramidal cell field, dentate gyrus, and layer 2 of the piriform cortex. For those regions, the appearance of autoradiograms prepared from rats killed 5 min after administration of [14C]2-deoxyglucose is remarkably similar to the appearance of autoradiograms prepared from rats killed 5 or 30 min after injection of [6(-14)C]glucose. Possible mechanisms are discussed to explain the observed differences in the accumulation of radioactivity in discrete brain regions after injection of [6(-14)C]glucose and [14C]2-deoxyglucose at the different survival times examined.

Animals↗

The metabolism of a physiological dose of radioactive cholecalciferol (vitamin D3) to its hydroxylated metabolites in man.

1. The metabolism of an intravenous pulse-dose of 65 nmol (25 microgram) of double-isotope-labelled cholecalciferol has been studied in 28 individuals. The subjects comprised 19 with serum concentrations of 25-hydroxycalciferol (25-(OH)D) less than or equal to 25 nmol/l, of whom 12 had clinical osteomalacia, and nine with serum 25-(OH)D > 25 nmol/l (30-125 nmol/l). 2. The concentrations in serum of radioactive cholecalciferol, 25-hydroxycholecalciferol (25-(OH)D3) and the three dihydroxylated metabolites: 1,25-, 24,25- and 25,26-dihydroxycholecalciferol (1,25-(OH)2D3, 24,25-(OH)2D3 and 25,26-(OH)2D3) were measured for up to 10 days after the injection. 3. The temporal relationships between the formation of individual radioactive metabolites and factors apparently influencing their production are described and their molar concentrations in serum calculated. 4. Formation of radioactive 1,25-(OH)2D3 was detectable only in vitamin D-deficient subjects. Between individuals, its maximum serum concentration was correlated significantly and inversely with serum calcium but with not other measured variable. In the individual, concentrations of radioactive serum 1,25-(OH)2D3 varied directly with radioactive serum 25-(OH)D3. 5. The failure to detect formation of radioactive 1,25-(OH)2D3 in vitamin D-replete subjects suggests that current estimates of the daily turnover of the hormone in the normal individual may be severalfold too high. 6. Radioactive 25,26-(OH)2D3 was produced rapidly by all subjects and in greater amounts by vitamin D-deficient individuals. Between subjects and in the individual its concentration in serum correlated only with the radioactive serum 25-(OH)D3. Production of this metabolite appeared to be unregulated and dependent solely on the concentration of its precursor. 7. In vitamin D-replete subjects, production of 24,25-(OH)2D3 was also apparently determined by precursor concentration. In vitamin D-depleted subjects, production of radioactive 24,25-(OH)2D3 was variably delayed for up to or more than 10 days. 8. There appeared to be a constraint on the quantitative hepatic production of 25-(OH)D which is not explained by simple feed-back inhibition. 9. If sterols other than 1,25-(OH)2D3 are required to initiate the mineralization of osteomalacic bone, after correction of vitamin D deficiency in man, 25-(OH)D3 and 25,26-(OH)2D3 are produced sufficiently rapidly to meet this hypothetical requirement, but not 24,25-(OH)2D3.

Cholecalciferol↗

Radioisotopic studies of the binding, exchange, and distribution of 5-hydroxytryptamine synthesized from its radioactive precursor.

1. The synthesis, distribution, storage, and subsequent metabolism of 5-hydroxytryptamine (5-HT) produced in mice from the administration of its radioactive precursor, 5-hydroxytryptophan, has been investigated to form the basis for a similar study to be conducted by radioautography.2. Intravenous injection of the radioactive material was found to be essential for significant uptake of radioactivity by tissue. The duration of the period during which radioactive material was available for uptake by the tissue was 2 hr.3. The relative distribution of radioactivity in individual organs was studied and the radioactive compounds present in each were identified and quantitatively assayed. No unrelated routes of metabolism of the labelled material were found and radioautographic results may be interpreted in terms of the metabolic picture which emerged.4. Radioactive 5-HT was bound in tissues in preference to both its precursor, and metabolite, 5-hydroxytryptamine-O-glucuronide, and the radioactive 5-HT produced in vivo after the injection of labelled 5-hydroxytryptophan probably entered and labelled the endogenous 5-HT pool.5. Fixatives prepared with buffer solutions made hypertonic by the addition of sucrose could rapidly and effectively halt the movement of radioactive 5-HT out of tissues and prevent its subsequent extraction during histological processing.6. It is concluded that localization of sites concerned with 5-HT metabolism by means of radioautography is feasible and the 5-HT so localized will probably reflect the physiological compartmentalization of the amine.

5-Hydroxytryptophan↗

Interaction of colicins with bacterial cells. I. Studies with radioactive colicins.

Maeda, Akio (Department of Genetics, University of Wisconsin, Madison), and Masayasu Nomura. Interaction of colicins with bacterial cells. I. Studies with radioactive colicins. J. Bacteriol. 91:685-694. 1966.-By use of a preparation of radioactive colicin E2, the following conclusions, which had been obtained previously from indirect experiments, were tested directly: (i) colicin stays at the receptor site on the cell and acts from there; (ii) colicins E2 and E3 share the same receptor, although their mode of action is entirely different; (iii) colicinogenic cells adsorb homologous colicin, although they are resistant to that colicin. Our experimental results confirmed the above conclusions. When sensitive cells of Escherichia coli K-12 pretreated with radioactive E2 were disrupted with a French pressure cell, and fractionated by differential centrifugation, it was found that most of the radioactivity stayed with the cell envelope fraction. Trypsin removed a major part of radioactivity from cells pretreated with radioactive E2, as was expected from the previous experiments on trypsin reversal of colicin action. Furthermore, it was shown that the trypsin treatment causes a recovery of the capacity of E2-pretreated cells to adsorb further colicin E2. When cells were first treated with various amounts of nonradioactive E3, and then treated with radioactive E2, the amount of radioactive E2 adsorbed was found to be inversely related to the amount of nonradioactive E3 adsorbed first. It was also shown that E2-colicinogenic cells adsorb radioactive E2, and yet are resistant to this colicin.

Adsorption↗

Quantitative aspects of the excretion of radioactive and microbiologically active material in urine after parenteral hydroxocobalamin.

The radioactive material in urine after parenteral radioactive hydroxocobalamin is composed of radioactive cyanocobalamin, radioactive hydroxocobalamin, and a radioactive anionic complex. Studies in vitro suggest that these materials have a similar microbiological activity. Comparison of the amounts of radioactive and microbiologically active material in urine after parenteral radioactive hydroxocobalamin show a significant correlation both in the first and second 24 hours after injection showing that the amount of radioactivity is an acceptable measure of the loss of cobalamin in urine. The slope of the regression lines obtained from cobalamin-deficient and normal subjects implies that there is no equilibration of injected radioactive hydroxocobalamin and body stores: this may be due to the absence of hydroxocobalamin from tissues or to the fact that tissue hydroxocobalamin is bound and incapable of equilibration.

Hydroxocobalamin↗

Distribution of radioactive silver in the subcellular fractions of various tissues of the rat and its binding to low molecular weight proteins.

In view of the electron microscopic evidence that silver does not penetrate cellular barriers, the distribution of radioactive silver in rat blood and subcellular fractions of liver, kidneys, spleen, and forebrain was studied. It was found that 24 h after a single intraperitoneal injection high levels of radioactivity were reached which decreased at different rates in the various tissues studied. In plasma, liver, and kidneys there was an initial rapid loss of radioactivity which was followed by a slower rate of loss. In the blood, forebrain, and spleen the loss of radioactivity was linear and somewhat slower than in the other three tissues. The cytosols of the liver and kidneys contained 60% while those of the forebrain and spleen contained 30% of the total radioactivity found in the tissue homogenates. Gel filtration on Sephadex G-75 showed that all cytosols contained two peaks of radioactivity; a high molecular weight peak which eluted just after the void volume and a low molecular weight peak. The amount of radioactivity in both peaks was, however, much lower in the chromatographic peaks of the forebrain and spleen than that found in those of the liver and kidneys. Furthermore, the spleen had a comparatively very small low molecular weight radioactive peak. In vitro experiments with liver cytosol showed similar results to those found in vivo in that the high molecular weight radioactive peak could be removed by heat. It is concluded that silver does enter cells and that silver thionein exists in the cytosols of forebrain, spleen, kidney, and liver.

Animals↗

Factors influencing serial measurements of cardiac volumes by count-based methods: effects of elevated catecholamines, position, and exercise on technetium-99m-blood radioactivity concentration.

Most radionuclide methods for measuring cardiac volume require a determination of the blood radioactivity concentration. Thus, changes in blood radioactivity over time or during interventions might lead to spurious volume estimates unless blood radioactivity is serially measured. The effects of elevated epinephrine, posture and exercise on 99mTc-labeled blood radioactivity concentration were studied in 15 young (mean age = 28 yr) and 14 older (mean age = 68 yr) healthy males. An epinephrine infusion of 50 ng/kg/min resulted in a 4.1% +/- 1.0% increase in 99mTc-blood radioactivity (p less than or equal to 0.001) compared to baseline. Sitting increased blood radioactivity concentration by 12.3% +/- 3.0% (p less than 0.0002) compared to the supine position and peak supine bicycle exercise caused an 11.0% +/- 1.7% increase (p less than or equal to 0.0001) compared to supine rest. There was a significantly greater increase during peak supine exercise in the young compared to the older subjects (15.0% +/- 2.3% versus 6.3% +/- 2.0%, p less than or equal to 0.01). The mechanism of the increase in blood radioactivity concentration is uncertain, but presumably reflects the addition of hemoconcentrated red blood cells from the spleen and/or the loss of plasma volume. Failure to correct for the increased blood radioactivity concentration during exercise or pharmacological interventions will result in a significant error in serial measurements of cardiac volumes by methods requiring RBC radioactivity measurements.

Adult↗

The radiological exposure of man from radioactivity in the Baltic Sea.

A radiological assessment has been carried out considering discharges of radioactivity to the Baltic Sea marine environment since 1950. The sources of radioactivity that have been evaluated are atmospheric nuclear-weapons fallout, fallout from the Chernobyl accident in 1986, discharges of radionuclides from Sellafield and La Hague transported into the Baltic Sea, and discharges of radionuclides from nuclear installations located in the Baltic Sea area. Dose rates from man-made radioactivity to individual members of the public (critical groups) have been calculated based on annual intake of seafood and beach occupancy time. The dose rates to individuals from the regions of the Bothnian Sea and Gulf of Finland are predicted to be larger than from any other area in the Baltic Sea due to the pattern of Chernobyl fallout. The dose rates are predicted to have peaked in 1986 at a value of 0.2 mSv year-1. Collective committed doses to members of the public have been calculated based on fishery statistics and predicted concentrations of radionuclides in biota and coastal sediments. The total collective dose from man-made radioactivity in the Baltic Sea is estimated at 2600 manSv, of which approximately two-thirds originate from Chernobyl fallout, approximately one-quarter from atmospheric nuclear-weapons fallout, approximately 8% from European reprocessing facilities, and approximately 0.04% from nuclear installations bordering the Baltic Sea area. An assessment of small-scale dumping of low-level radioactive waste in the Baltic Sea in the 1960s by Sweden and the Soviet Union has showed that doses to man from these activities are negligible. Dose rates and doses from natural radioactivity dominate except for the year 1986 where dose rates to individuals from Chernobyl fallout in some regions of the Baltic Sea approached those from natural radioactivity.

Baltic States↗

Over the border--the problems of uncontrolled radioactive materials crossing national borders.

Cross-border movement of radioactive materials and contaminated items, in particular metallurgical scrap, has become a problem of increasing importance. Radioactive sources out of regulatory control, now often called 'orphan sources', have frequently caused serious, even deadly, radiation exposures and widespread contamination. The United States Nuclear Regulatory Commission reported over 2,300 incidents of radioactive materials found in recycled metal scrap and more than 50 accidental smeltings of radioactive sources. A further potentially serious problem is illicit trafficking in nuclear and other radioactive materials. In 1995 the International Atomic Energy Agency (IAEA) started a programme to combat illicit trafficking in nuclear and other radioactive materials, which includes an international database on incidents of illicit trafficking, receiving reports from some 80 member states. For the period 1993-2000 the IAEA database includes 345 confirmed incidents. While from 1994-1996 the frequency declined significantly, this trend has been reversed since 1997, largely due to radioactive sources rather than nuclear material. This paper compares monitoring techniques for radioactive materials in scrap applied at steel plants and scrap yards with monitoring at borders, a completely different situation. It discusses the results of the 'Illicit Trafficking Radiation Detection Assessment Program', a large international pilot study, conducted in cooperation between the IAEA, the Austrian Government and the Austrian Research Centre Seibersdorf. The aim of this exercise was to derive realistic and internationally agreed requirements for border monitoring instrumentation. Finally the present extent of border monitoring installations is discussed.

Crime↗

Risk-informed radioactive waste classification and reclassification.

Radioactive waste classification systems have been developed to allow wastes having similar hazards to be grouped for purposes of storage, treatment, packaging, transportation, and/or disposal. As recommended in the National Council on Radiation Protection and Measurements' Report No. 139, Risk-Based Classification of Radioactive and Hazardous Chemical Wastes, a preferred classification system would be based primarily on the health risks to the public that arise from waste disposal and secondarily on other attributes such as the near-term practicalities of managing a waste, i.e., the waste classification system would be risk informed. The current U.S. radioactive waste classification system is not risk informed because key definitions--especially that of high-level waste--are based on the source of the waste instead of its inherent characteristics related to risk. A second important reason for concluding the existing U.S. radioactive waste classification system is not risk informed is there are no general principles or provisions for exempting materials from being classified as radioactive waste which would then allow management without regard to its radioactivity. This paper elaborates the current system for classifying and reclassifying radioactive wastes in the United States, analyzes the extent to which the system is risk informed and the ramifications of its not being so, and provides observations on potential future direction of efforts to address shortcomings in the U.S. radioactive waste classification system as of 2004.

Decision Making↗

Effect of atropine and gammahydroxybutyrate on ischemically induced changes in the level of radioactivity in [3H]inositol phosphates in gerbil brain in vivo.

Brain ischemia in gerbils was induced by ligation of both common carotid arteries for 1 min or 10 min. Sham-operated animals served as controls. Intracerebral injection of [3H]inositol into gerbil brain 16 hr before ischemic insult resulted in equilibration of the label between inositol lipids and water-soluble inositol phosphate. A short ischemic period (1 min) resulted in a statistically significant increase in the radioactivity of inositol triphosphate (IP3) and inositol monophosphate (IP), by about 48% and 79%, respectively, with little change in that of the intermediate inositol biphosphate (IP2), which increased by about 16%. When the ischemic period was prolonged (10 min), an increase in the radioactivity of inositol monophosphate exclusively, by about 84%, was observed. The level of radioactivity in inositol phosphates IP2 and IP3 decreased by about 50%, probably as a consequence of phosphatase activation by the ischemic insult. The agonist of the cholinergic receptor, carbachol, injected intracerebrally (40 micrograms per animal) increased accumulation of radioactivity in all inositol phosphates. The level of radioactivity in IP3, IP2, and IP was elevated by about 40, 23, and 147%, respectively. The muscarinic cholinergic antagonist, atropine, injected intraperitoneally in doses of 100 mg/kg body wt. depressed phosphoinositide metabolism in control animals. The level of radioactivity in water-soluble inositol metabolites in the brain of animals pretreated with atropine was evidently about 32% lower than in untreated animals. Pretreatment with atropine decreased the radioactivity of all inositol phosphates in the brain of animals subjected to 1-min ischemia and the radioactivity of IP in the case of 10-min brain ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Tissue distribution and excretion of radioactively labelled compounds in the Wistar rat after administration of [N-methyl-14C]-erythromycin A.

Tissue distribution and excretion of radioactively labelled compounds was studied in the Wistar rat after i.v. administration of [N-methyl-14C]-erythromycin A. Whole-body autoradiography and liquid scintillation counting was used to investigate the tissue localization of radioactivity in pregnant and non-pregnant rats. Tissue levels were maximal within 20 min, except for lachrymal glands, thymus and brain. Large amounts of radioactively labelled compounds, partly originating from active secretion, were present in the small intestine and caecum. Marked concentration of radioactively labelled compounds was also observed in the liver, spleen, lachrymal and salivary glands, lymph nodes, mammary glands, skin, bone marrow, and, to a lesser extent, in the lung, kidney and skeletal muscle. During six hours of experimental follow-up, plasma levels remained lower than corresponding tissue levels. At 1 h the radioactivity in fetuses was about three times lower than that in maternal blood. Within 48 h, more than 90% of the administered radioactivity was excreted. The amounts of radioactivity recovered in urine, faeces and expired air were about 19%, 48% and 24% respectively. After 48 h, 8% of the administered radioactivity was found in the carcass.

Animals↗

Radioactive isotope uptake in a grass-legume association.

The radioactive uptake of Medicago sativa and Rye grass in a pasture exposed to the fallout from the Chernobyl reactor accident, was determined in four consecutive harvests covering a period of one year after the accident,In plants of Medicago sativa, inoculated with an effective Rhizobia meliloti strain isolated from Greek soils, a high degree of biological nitrogen fixation was observed at all harvests using N-15 techniques. At the second and third harvests, the percentage nitrogen derived from fixation (%NdfF), the percentage nitrogen derived from soil (%NdfS), as well as the radioactive uptake from the soil remained stable. At the fourth harvest, however, the %NdfF decreased while the %NdfS and the radioactive uptake from soil significantly increased. At the first harvest the radioactivity in both plants, caused mainly by direct fallout contamination, was considerably higher than that observed at the later harvests. Medicago sativa contained significantly less radioactivity than the grass at all harvests, although both plants were grown under the same environmental conditions. Even at the fourth harvest, almost one year after the initial contamination, the radioactivity of grass remained at high levels ( 20 Bq g(-1) of protein) while in Medicago sativa it assumed considerably lower values (3.6 Bq g(-1) of protein). A possible involvement of biological nitrogen fixation in the reduction of radioactive uptake is discussed. Finally, certain practical conclusions are drawn with respect to a safer management of pastures exposed to radioactivity.

Journal Article↗

A newly designed radioimmunoconjugate releasing a hippurate-like radiometal chelate for enhanced target/non-target radioactivity.

Target-to-non-target ratio of radioactivity can be enhanced by the injection of monoclonal antibodies (MoAbs) labeled with metallic radionuclides, if some modality to accelerate the urinary excretion of radioactivity accumulated in non-target tissues could be introduced. In this study, a radioimmunoconjugate chemically designed to release a hippurate-like radiometal chelate was synthesized and tested in vivo. A 67Ga chelate of succinyldeferoxamine (SDF) was conjugated with a MoAb against osteogenic sarcoma (OST7, IgG1) through an ester bond using a new metabolizable MESS linker, N-[I4-(maleimidoethoxy)succinyl]oxy]succinimide (67Ga-DFO-MESS-OST7). When injected into normal mice, 67Ga-DFO-MESS-OST7 exhibited faster clearance of radioactivity from circulation with less accumulation in the liver, kidney and spleen than those observed with 67Ga-DFO-EMCS-OST7, which was prepared under identical conditions to 67Ga-DFO-MESS-OST7 except for using a non-metabolizable linker holding no ester bond to release 67Ga-SDF. Size exclusion HPLC analysis of the liver homogenate obtained from mice 24 h after injection of 67Ga-DFO-MESS-OST7 indicated that all the radioactivity was eluted in the high molecular weight fraction with most of it being present as the 67Ga-DFO-MESS-OST7 fraction. Reverse-phase HPLC analysis of urine sample from the same mice showed a single radioactivity peak at the same retention time as that of 67Ga-SDF. In athymic mice bearing osteogenic sarcoma, 67Ga-DFO-MESS-OST7 exhibited higher tumor-to-blood and tumor-to-organ ratio of radioactivity when compared with 67Ga-DFO-EMCS-OST7. These results indicated that 67Ga-DFO-MESS-OST7 achieved enhanced target-to-non-target ratio of the radioactivity, due to preferential cleavage of the ester bond in non-target tissues, followed by rapid urinary excretion of the resulting chelate (probably as 57Ga-SDF). These results also suggest that the present design would become an applicable modality for enhancing the target-to-non-target ratio of radioactivity by MoAbs.

Animals↗

Dose and dose rate effects of beta-particle emitting radioactive stents in a porcine model of restenosis.

BACKGROUND: Radioactive stents have been proposed as a means to prevent in-stent restenosis by inhibiting intimal proliferation with continuous low-dose irradiation. OBJECTIVES: The purpose of this study is to determine the effects of cumulative dose and dose-rate delivery on neointimal formation using 32P and 90Y beta-particle emitting radioactive stents in a porcine coronary model of restenosis. METHODS AND MATERIALS: We compared the late histologic results of 0.25 to 32.0 microCi 90Y (half-life 64 hours) (n = 64 stents) and 0.1 to 57.6 microCi 32P (half-life 14.3 days) (n = 55 stents) Beta-particle emitting radioactive stents with non-radioactive (n = 40) stents in a porcine coronary model of restenosis. A computer-based dosimetry modeling program was used to determine the 28 day cumulative dose and dose-rate delivery for the beta-particle emitting radioactive stents at a distance of 0.1 mm from the stent surface. RESULTS: Continuous low dose-rate (1 to 5 cGy/hr) radiation delivery for > 2 weeks via a 0.1 to 0.5 microCi 32P radioactive stent effectively reduced in-stent neointimal hyperplasia at 90 days. Cumulative doses of > 55 Gy induced severe adventitial fibrosis, microvascular damage and promoted the formation of a matrix-rich neointima. Delayed vascular repair was evident at focal regions within the body of radioactive stents that delivered cumulative doses of > or = 140 Gy at 28 days and cumulative doses of 1,100 Gy at 90 days. CONCLUSIONS: These data may be useful in predicting safe and effective dose and dose rate delivery for beta-particle emitting radioactive stents.

Animals↗

Use of radioactive glucosamine in the perfused rat liver to prepare alpha 1-acid glycoprotein (orosomucoid) with 3H- or 14C-labelled sialic acid and N-acetylglucosamine residues.

1. A method was developed whereby [1-14C]glucosamine was used in a perfused rat liver system to prepare over 2 mg of alpha 1-acid glycoprotein with highly radioactive sialic acid and glucosamine residues. 2. The liver secreted radioactive alpha 1-acid glycoprotein over a 4-6 h period, and this glycoprotein was purified from the perfusate by chromatography on DEAE-cellulose at pH 3.6. 3. The sialic acid on the isolated glycoprotein had a specific radioactivity of 3.1 Ci/mol, whereas the glucosamine-specific radioactivity was 4.3 Ci/mole. The latter amino-sugar residues on the isolated protein were only 13-fold less radioactive than the initially added [1-14C]glucosamine. Orosomucoid with a specific radioactivity of 31.3 microCi/mg of protein was obtainable by using [6-3H]glucosamine. 4. The amino acid composition of the purified orosomucoid was comparable with that found by others for the same glycoprotein isolated from rat serum. A partial characterization of the carbohydrate structure was done by sequential digestion with neuraminidase, beta-D-galactosidase and beta-D-hexosaminidase. 5. Many other radioactive glycoproteins were found to be secreted into the perfusate by the liver. Thus this experimental system should prove useful for obtaining other serum glycoprotein with highly radioactive sugar moieties.

Amino Acids↗