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PubMed1996

Management of thyroid carcinoma with radioactive 131I.

PURPOSE: To evaluate the role of radioactive 131I in the management of patients with well differentiated carcinoma of the thyroid. METHODS AND MATERIALS: Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131I. RESULTS: With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131I therapy. CONCLUSIONS: Radioactive 131I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131I.

Adolescent↗
PubMed1986

High-performance liquid chromatographic on-line flow-through radioactivity detector system for analyzing amino acids and metabolites labeled with nitrogen-13.

A flow-through radioactivity detector was used for the high-performance liquid chromatographic determination of amino acids and other nitrogenous substances labeled with 13N, a short-lived (t1/2 9.96 min) positron-emitting radionuclide. 13N-Labeled compounds were analyzed using cation, anion and amino columns, or as the o-phthaldialdehyde derivative on an ODS column. Use of column-switching valves and a high-performance liquid chromatographic system with a quaternary eluting capability permits two to three 20-min analyses of labeled samples from a single 13N experiment to be carried out on different columns using a binary or a single mobile phase. Radioactivity in liver metabolites was quantified using an on-line flow-through monitor with data processing capability for integrating peaks and correcting for radioactivity decay. As an example, 1 min following an L-[13N]glutamate injection via the hepatic portal vein, 77% of the label in the liver was in a metabolized form; at least ten labeled products were formed.

Amino Acids↗
PubMed1997

Narrow-bore liquid chromatography-tandem mass spectrometry with simultaneous radioactivity monitoring for partially characterizing the biliary metabolites of an arginine fluoroalkyl ketone analog of D-MePhe-Pro-Arg, a potent thrombin inhibitor.

Characterizing components eluting from a HPLC column is enhanced when multiple detectors are incorporated in-line. The performance of a system consisting of a combination of two detectors-electrospray ionization mass spectrometry (and tandem mass spectrometry) and radioactivity monitoring, following gradient separation with a 250 x 2.1 mm I.D. (Vydac Protein and Peptide C18, 5 microns, 300 A) column-is evaluated with respect to chromatographic integrity and detection. The HPLC effluent was split (8:1) and a post-column make-up solvent was added to flow directed towards the radioactivity detector containing a solid glass cell. Trifluoracetic acid (0.1%) was added to the make-up flow solvent to prevent silanol interactions from degrading the profile displayed in the 14C trace. A 14C chromatographic peak representing 550 dpm was detected with signal-to-noise ratio of 3. This system was used for rapidly characterizing the biliary metabolites of an arginine fluoroalkyl ketone analog of D-MePhe-Pro-Arg, a potent thrombin inhibitor currently being evaluated as a drug candidate. These metabolites are shown to comprise of mono- and dihydroxylated drug as well as a reduced ketone form of the drug. Combining the radioactivity monitor in-line with the mass spectrometer ensured that all of the major metabolites (as evident from the 14C profile) were characterized by mass spectrometry.

Amino Acid Chloromethyl Ketones↗
PubMed1999

On the use of liquid chromatography with radio- and ultraviolet absorbance detection coupled to mass spectrometry for improved sensitivity and selectivity in determination of specific radioactivity of radiopharmaceuticals.

Pneumatically assisted electrospray mass spectrometry was evaluated as a complementary detection technique to UV absorbance, for determination of specific radioactivity of tracer molecules to be used in positron emission tomography. Tracers labelled with radionuclides having short half-lives can be synthesised with high specific radioactivity. The UV absorbance detection that is commonly used for the determination does not always have the sensitivity required for those analyses. In comparison, mass spectrometry gave improved detection limits in all but one (nicotine) of the 12 compounds studied. The magnitude of this improvement was more than 100-fold for the compounds ketamine (2-methylamino-2-(2-chloro-phenyl)cyclohexanone), SCH-23390 ((R)-(+)-7-chloro-8-hydroxy-1-methyl-1-phenyl-2,3,4,5-tetra-hydro-1H-3-b enzazepine) and N-methyl-piperidylbenzilate. These improved detection limits, specificity, plus the added certainty of product identity provided by mass spectral data demonstrated the value of the mass spectrometer as a complementary detector in the determination of specific radioactivity.

Chromatography, Liquid↗
PubMed2001

Stability of biodegradable radioactive rhenium (Re-186 and Re-188) microspheres after neutron-activation.

Our objective was to determine if microspheres made from the biodegradable polymer poly(lactic acid) that contained rhenium could withstand the conditions of direct neutron activation necessary to produce therapeutic amounts of radioactive rhenium. The radiation damage of the polymer produced by gamma-doses of up to 1.05 MGy from Re-186 and Re-188 was examined by scanning electron microscopy and size exclusion chromatography. At a thermal neutron flux of 1.5 x 10(13)n/cm2/s the microspheres melted after 3 h in the nuclear reactor, but suffered little damage after 1 h of radiation and released less than 5% of the radioactivity during incubation in buffer at 37 degrees C. The radioactive microspheres produced in this manner have a specific activity too low for radioembolization for treatment of liver tumors, but could be injected directly into tumors or applied topically to the wound bed of partially resected tumors.

Biodegradation, Environmental↗
PubMedDate not supplied

A dual-compensated cryogenic microcalorimeter for radioactivity standardizations.

Efforts are underway by our laboratory to develop a microcalorimeter that can be routinely used for radioactivity standardizations of nuclides that decay by pure beta-emission or by low-Z electron capture. The prototype calorimeter consists of a cryostat with two temperature-controlled stages and a base stage that are operated at nominal temperatures of 8 K. A unique aspect of the calorimeter's design is the ability to repeatedly engage and disengage the radioactive source from the second stage heat path using a magnetically activated elevator. The measurement of the total power from a radioactive sample is obtained from the difference in the second stage power with and without the source in place. As a result of extensive performance evaluations using 90Sr-90Y and 32P brachytherapy seeds as well as with an internal calibration heater, many initial design flaws have been identified and are being addressed.

Journal Article↗
PubMedDate not supplied

Results from APMP comparisons on radioactivity measurements of 58Co, 88Y and 166mHo.

International comparisons on radioactivity measurements of 55Co, 88Y and 166mHo were carried out within the framework of the Asia-Pacific Metrology Programme. Radioactive sources were also sent to the International Reference System (SIR) at the Bureau International des Poids et Mesures (BIPM) in order to link the results of these regional comparisons to the BIPM key comparison-reference values. The arithmetic mean for the activity results of 166mHo was in good agreement with the SIR reference value, but some disagreements were found for 58Co and 88Y results. The mean values for 58Co and 88Y were both higher than the existing SIR values by about 1.5% and 0.9%, respectively. Although there were some disagreements, it was successfully demonstrated that these regional comparisons could be linked to other international key comparisons through the SIR. The present results were also evaluated to estimate a reasonable uncertainty level for each laboratory, which is very important in the establishment of an adequate traceability scheme for radioactivity standards.

Journal Article↗
PubMed2002

Radioactivity concentrations in sediments and their correlation to the coastal structure in Kuwait.

Gamma-ray spectrometric measurements were performed on sediment samples from the coast of Kuwait to study the concentration of natural as well as man-made radioactive sources. The coast of Kuwait, which extends for some 170 km is mainly soft sedimentary colitic limestones or sandstones, overlaid in many areas with beach or wind-blown sand. In the north, suspended material from the Shatt Al-Arab delta has settled to form extensive soft areas of intertidal mud within Kuwait Bay. Forty samples were taken at different points along the coast in undisturbed areas at intervals of about 5 km. Collection was carried out during low-tide, where it was possible to collect sediments from the wet region that was covered by seawater during the high tide. At each of the sample sites, a sampling area of about 1 m2 was considered. Samples collected from the north were of a muddy nature, whereas the southern samples were sandy. All samples were left to dry in open air before drying in the oven at 105 degrees C for 2-3 days to remove all water content. The radioactivity in southern areas reaches about one half of the values commonly assigned as the world average. In the northern areas, higher radioactivity concentrations are found but are still below the international levels.

Cesium Radioisotopes↗
PubMed1998

The state-of-the-art on worldwide studies in some environments with elevated naturally occurring radioactive materials (NORM).

Direct observations and studies of the radiobiological and epidemiological effects of ionizing radiation from naturally occurring radioactive materials (NORM) on man, in particular in areas with elevated NORM, are becoming of prime concern in radiation protection. This is due to existing discrepancies in the application of the linear no-threshold theory in obtaining radiation risks at low doses by extrapolation from high dose to low dose using dose and dose-rate effective factors. Many areas in the world have elevated NORM caused either by the geological and geochemical structure of the soil, or by the radioactive content of the water flowing from hot springs and/or due to technologically enhanced radioactivity as well as due to cosmic rays. Such areas, with relatively large cohort sizes, have been the subject of intensive dosimetry, radiobiological and epidemiological studies. It is the purpose of this article to review: sources of NORM and human exposure, needs and problems in study of areas with elevated NORM; the criteria for their classification; some areas with elevated NORM and the results of related studies, and some conclusions and recommendations for unification of an approach in future studies aimed at obtaining better estimates of human radiation risk factors from the effects of ionizing radiation.

Background Radiation↗
PubMed1999

Production of radioactive endovascular stents by implantation of 133Xe ions.

A coronary stent was made radioactive by implantation of 133Xe ions for the purpose of suppressing the renarrowing of the part of blood vessel in which the stent is implanted. Electrons of relatively low energies emitted in the decay of 133Xe may give an antiproliferative effect of ionizing radiation to the intimal cells within a limited range of 1 mm. A 133Xe+ beam accelerated at 40 or 60 keV was directed to several stainless steel stents mounted on a target-holder table that could revolve and move up and down to distribute the 133Xe+ ions within a stent as well as among the stents. The radioactive stents produced contained up to 100 kBq of 133Xe and were implanted into the abdominal aortas of rabbits. Neointimal thickening was analyzed by histomorphometry for samples taken 4 weeks after stent implantation. The results indicate that the radioactive stents have a potential to suppress neointimal hyperplasia in rabbits.

Angioplasty, Balloon, Coronary↗
PubMedDate not supplied

Methods to improve dose uniformity for radioactive stents in endovascular brachytherapy.

Intravascular brachytherapy (IVBT) has rapidly gained acceptance as a new treatment modality for reducing restenosis and improving the success rate of percutaneous transluminal coronary angioplasty (PTCA). Recent clinical results on patients treated with beta-emitting 32P stents suggest that radiation reduces in-stent restenosis but may exacerbate neointimal growth at the edges of the stents. This has been referred to as the "candy wrapper effect." It is well known that radioactive stents yield extremely inhomogeneous dose distributions, with low doses delivered to tissues in between stent struts, at the ends of the stent, and also at depth. Some animal model studies suggest that low doses of radiation may stimulate rather than inhibit neointimal growth in an injured vessel, and it is hypothesized that dose inhomogeneity at the ends of a stent may contribute to the candy wrapper effect. We present here a theoretical study comparing dose distributions for beta stents vs. gamma stents; "dumbbell" radioactive loaded stents vs. uniformly loaded stents; and stents with alternate strut design. Calculations demonstrate that dose inhomogenieties between stent struts, at the ends of stents, and at depth can be reduced by better stent design and isotope selection. Prior to the introduction of radioactive stents, criteria for stent design included factors such as trackability, flexibility, strength, etc. We show here that if stent design also includes criteria for strut shape and spacing that improved dose distributions are possible, which in turn could reduce the candy wrapper effect.

Angioplasty, Balloon, Coronary↗
PubMed1989

Phospholipid metabolism in Plasmodium-infected erythrocytes: guidelines for further studies using radioactive precursor incorporation.

The biosynthesis of phospholipids is extensive in Plasmodium knowlesi-infected simian erythrocytes due to the synthesis of membranes by this single-cell eukaryote in a host erythrocyte devoid of any pathway for lipid biosynthesis. In the present paper, we show that the incorporation of [3H]glycerol, which reflects de novo biosynthesis, is better studied at 300 microM-1 mM than at the trace doses, since this non-physiological precursor does not modify the amount of phosphatidylcholine biosynthesis from [3H]choline. Time-course incorporation of radioactive glycerol, oleate, lysophosphatidylcholine, choline, and inositol in RPMI 1640 medium containing nutrients for lipid synthesis showed that the optimum incubation time for phospholipid studies is 60-90 min, after which radioactive incorporation slows considerably. On the other hand, studies with [14C]serine revealed that incubation for 2-3 h is necessary for isotopic labelling of phosphatidylcholine via phosphatidylserine decarboxylation and phosphatidylethanolamine N-methylation. Incorporation of the various fatty acids into individual lipids was related to the molecular species composing each of them. Studies with [14C palmitoyl] lysophosphatidylcholine showed a very fast intracellular release of radioactive fatty acids, which indicates a potent lysophospholipase activity. Taken together, these data define the indispensable conditions for an experimental system suitable for further studies.

Animals↗
PubMedDate not supplied

Differential radioactive proteomic analysis of microdissected renal cell carcinoma tissue by 54 cm isoelectric focusing in serial immobilized pH gradient gels.

We present a proof of principle study, using laser microdissection and pressure catapulting (LMPC) of two clinical tissue samples, each containing approximately 3.8 microg renal cell carcinoma protein and 3.8 microg normal kidney protein respectively from one patient. The study involved separate radio-iodination of each sample with both (125)I and (131)I, dual inverse replicate sample loading to high resolution 54 cm "daisy chain" serial immobilized pH gradient isoelectric focusing (IPG-IEF) 2D-PAGE gels, co-electrophoretic separation of cross-labeled proteins from different samples, and precision multiplex differential radioactive imaging to obtain signals specific for each sample coelectrophoresed within single gels but labeled with different isotopes of iodine, providing extremely precise intra-gel estimates of the abundance ratio for protein spots from both samples. Twelve multiplexed analytical radioactive SDS-gels from 4 serial IPG-IEF gels provided 24 individual radioactive images for a comprehensive analytical protein multiplex quantification study. A further 12 SDS gels containing (125)I-labeled sample were coelectrophoresed with preparative protein amounts obtained from whole tissue sections for the mass spectrometric identification of comigrating proteins. This consumed <40% of the (125)I-labeled sample, and <20% of the (131)I-labeled sample from the respective original 3.8 microg samples. Twenty-nine proteins were identified by mass spectrometry with PMF scores >70 that were >2-fold differentially abundant between the samples and t-test probabilities <0.05. We conclude that this combination of technologies provides excellent quality protein multiplex data for the differential abundance analysis of large numbers of proteins from extremely small samples, and is applicable to a broad range of clinical and related applications.

Carcinoma, Renal Cell↗
PubMed1981

Disposition of intravenous radioactive acyclovir.

The kinetic and metabolic disposition of (8-14C)acyclovir (ACV) was investigated in five subjects with advanced malignancy. The drug was administered by 1-hr intravenous infusion at doses of 0.5 and 2.5 mg/kg. Plasma and blood radioactivity-time, and plasma concentration-time data were defined by a two-compartment open kinetic model. There was nearly equivalent distribution of radioactivity in blood and plasma. The overall mean plasma half-life and total body clearance +/- SD of ACV were 2.1 +/- 0.5 hr and 297 +/- 53 ml/min/1.73 m2. Binding of ACV to plasma proteins was 15.4 +/- 4.4%. Most of the radioactive dose excreted was recovered in the urine (71% to 99%) with less than 2% excretion in the feces and only trace amounts in the expired Co2. Analyses by reverse-phase high-performance liquid chromatography indicated that 9-(carboxymethoxymethyl)guanine was the only significant urinary metabolite of ACV, accounting for 8.5% to 14.1% of the dose. A minor metabolite (less than 0.2% of dose) had the retention time of 8-hydroxy-9-[(2-hydroxyethoxy)methyl]guanine. Unchanged urinary ACV ranged from 62% to 91% of the dose. There was no indication of ACV cleavage to guanine. Renal clearance of ACV was approximately three times the corresponding creatinine clearances.

Acyclovir↗
PubMed1992

Neuroreceptor quantitation in vivo by the steady-state principle using constant infusion or bolus injection of radioactive tracers.

The approaches hitherto used for measuring the kinetic constants Kd and Bmax of neuroreceptors in vivo all violate the steady state of the system. This complicates the kinetic analysis as approximations must be made, introducing errors of unknown magnitude. The present study presents the theory for designing experiments in which the steady state is preserved. It is based on maintaining a constant degree of receptor binding (occupancy) throughout the experiment. This is achieved by administering by prolonged intravenous infusion the non-radioactive ligand one wishes to study. The fraction of receptors sites not occupied by the "cold" ligand is measured by using trace amounts of a radioactive ligand binding to the same receptor. A minimum of two studies at different occupanies must be performed. In this presentation it is proposed to make the second study at essentially zero receptor occupancy by administering the tracer alone. The pair of tracer studies, the one without and the other with infusion of cold ligand, allows calculation of the cold ligand's equilibrium dissociation constant Kd. In the special case when tracer and cold ligands are chemically identical, then Bmax can also be calculated. Two different modes of tracer administration can be used. If the tracer is also infused at a constant rate for a long time, then the occupancy of receptor sites by the cold ligand can be calculated by measuring the equilibrium tracer concentrations in brain and plasma. If the tracer is administered as an intravenous bolus injection, then the area under the brain and plasma radioactivity curves or compartmental analysis must be used.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1967

Effect of thrombin on the radioactive nucleotides of human washed platelets.

Radioactive ATP and ADP were found in platelets after incubation of human platelet-rich plasma with either [8-(14)C]adenosine or [8-(14)C]ADP. Treatment of the labelled and washed platelets with thrombin indicated that, though considerable amounts of ATP and ADP were released to the supernatant, radioactive ATP and ADP remained predominantly in the cellular fraction. Breakdown of radioactive ATP took place to form mainly IMP and hypoxanthine, the latter compound appearing in the supernatant. The results indicate the presence of at least two pools of nucleotide in platelets. Evidence is given that the two pools contain approximately the same amounts of ATP plus ADP, and that the ratio of ATP to ADP in the pool released to the supernatant by the action of thrombin is about 0.7-0.8.

Adenine Nucleotides↗
PubMed1972

Studies on gastric mucoproteins. The production of radioactive mucoproteins by pig gastric mucosal scrapings in vitro.

1. Optimum conditions, including the effect of media of different pH values, were determined for the incorporation of radioactive precursors into mucoproteins by pig gastric mucosa in vitro. 2. Mucosal scrapings incorporated radioactivity from [U-(14)C]-glucose and from [G-(3)H]threonine or [G-(3)H]serine solely into the carbohydrate and protein portions respectively of the mucoprotein molecules. 3. Of the radioactive mucoprotein 22% was water-soluble and up to 80% of the remainder was soluble in other solvents. 4. Pronase was the most successful proteolytic enzyme tested for making the mucoprotein water-soluble, up to 94% dissolving after digestion. 5. The Pronase digestion products of the mucoproteins were separated from protein by equilibrium-density-gradient centrifugation in a CsCl gradient. 6. These Pronase-digested mucoproteins were further fractionated on Sepharose 4B and the isolated fractions analysed by chemical and sedimentation-velocity methods. 7. Pronase digestion and solvent extraction of mucosal scrapings labelled with (14)C in the carbohydrate and (3)H in the protein showed that one type of mucoprotein was the only non-diffusible biosynthetic product of the scrapings in vitro, and that this mucoprotein was the only mucoprotein constituent of the water-soluble and water-insoluble mucus.

Animals↗
PubMed1979

Computed resolution and relative specific radioactivities of radiolabelled proteins synthesized by isolated gastric mucosal cells.

1. By radiolabelling, polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulphate and fluorography, more than 50 soluble proteins in the molecular-weight range 15000-100000 were shown to continue to be synthesized after cells had been isolated from rat gastric mucosa. 2. Densitometric measurements of stained gels and fluorographic films were processed by computer to resolve individual overlapping Gaussian peaks corresponding to the protein bands. 3. Comparison of resolved peak areas of radioactivity and staining showed certain bands to have characteristically high relative specific radioactivities. 4. The computer programs (in FORTRAN) permit the analysis of a single densitometric trace or the simultaneous comparison of a corresponding pair of densitometric records of stained gels, or of fluorographic films, or a combination. Central processing unit time is used economically. 5. The programs identify the Gaussian components that contribute to the records and estimate their means, standard deviations and enclosed areas. These estimates are improved by a piecewise iterative method that minimizes the errors between the calculated and the experimental data. 6. Relative specific radioactivities are calculated as the normalized ratio of the area of a fluorographic film peak and the area of the corresponding stained gel peak. The computer programs have been deposited as Supplementary Publication SUP 50094 (55 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms given in Biochem. J. (1978) 169, 5.

Animals↗