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Use of a stable copper isotope (65Cu) in the differential diagnosis of Wilson's disease.

1. 65Cu/63Cu stable-isotope ratios have been measured in blood serum after oral administration of the stable isotope 65Cu. The incorporation of the isotope into the plasma protein pool was followed at various times for up to 3 days. The resulting patterns of enrichment in healthy control subjects, in Wilson's disease patients and in heterozygotes for the Wilson's disease gene, were similar in appearance to those found by others using copper radioactive isotopes. After an initially high enrichment at 2 h after dosage, the Wilson's disease cases, in contrast to the control subjects, did not show a secondary rise in isotope enrichment of the plasma pool after 72 h, demonstrating a failure to incorporate copper into caeruloplasmin. The Wilson's disease heterozygotes had variable degrees of impairment of isotope incorporation, not always distinguished from those of control subjects. 2. The stability of the isotope also permits the copper tracer to be followed for a longer period. Ten healthy subjects were studied for over 40 days, allowing the biological half-time of an oral dose of copper to be determined (median 18.5 days, 95% confidence interval 14-26 days). Known heterozygotes for the Wilson's disease gene were found to have a significantly increased biological half-time for removal of copper from the plasma pool (median 43 days, 95% confidence interval 32-77 days). 3. The incorporation of 65 Cu in patients with diseases of the liver (other than Wilson's disease) was found to be similar to that in control subjects, aiding differential diagnosis.

Adolescent↗

Radioiodine therapy for hyperthyroidism.

Radioiodine (131I), a radioactive isotope of iodine, is widely used for the treatment of patients with thyroid disorders, particularly hyperthyroidism. Its use in hyperthyroidism has increased in the UK since we last reviewed this subject (e.g. from a total of 8,000 doses in 1982 to 10,000 in 2003/4). Here we reconsider the use of radioactive iodine in adults with hyperthyroidism, including how it compares with antithyroid drugs and surgery, the other therapies for hyperthyroidism.

Adult↗

CaNa2EDTA for improvement of radioimmunodetection and radioimmunotherapy with 111In and 90Y-DTPA-anti-CEA MAbs in nude mice bearing human colorectal cancer.

UNLABELLED: 111In and 90Y, dissociated from 111In-labeled-monoclonal antibody (MAb) and 90Y-labeled MAb, may cause deterioration of the image quality in radioimmunodetection (RID) and undesirable irradiation of nontargeted tissue in radioimmunotherapy (RIT), respectively. The aim of this study was to investigate any improvement in RID and RIT with 111In-MAb and 90Y-MAb by pre- and postadministration of calcium disodium ethylenetriaminetetraacetic acid (CaNa2EDTA). METHODS: Murine MAb F33-104 against carcinoembryonic antigen (CEA) was labeled with 111In or 90Y by the diethylenetriamine pentaacetic (DTPA)-anhydride method. The influence of CaNa2EDTA on loss of radioactivity from 111In-MAb or 90Y-MAb in serum was investigated in vitro. The effects of CaNa2EDTA, administered before and after 111In-MAb or 90Y-MAb, on the biodistribution of radioactive isotopes in nude mice bearing human colon adenocarcinoma LS 180 tumor expressing CEA, or human pulmonary carcinoma PC 9 tumor expressing no CEA, were then examined. As a control, 0.9% NaCl was used in both the in vitro and in vivo studies. RESULTS: CaNa2EDTA did not cause any decrease in levels of radioactivity of radiolabeled MAbs. Pre- and post-treatment with CaNa2EDTA reduced radioctivity in both specific and nonspecific tumors at 72 h after 111In-MAb injection resulting in an increase of the specific tumor-to-nonspecific tumor radioactivity ratio. The levels of hepatic and renal radioactivity were also subsequently decreased by CaNa2EDTA. On the other hand, CaNa2EDTA pre- and post-treatment reduced levels of bony, hepatic, and renal radioactivity at 24, 72, and 72 h, respectively, after 90Y-MAb injection, although it had no effect on tumor radioactivity. CONCLUSION: Pre- and post-treatment with CaNa2EDTA would be of great use in humans who undergo RID or RIT with 111In-MAb and 90Y-MAb accompanied by disassociation of the labeled radionuclides.

Animals↗

Absorption of strontium from the gastrointestinal tract into plasma in healthy human adults.

The radioactive isotopes of strontium have always been a major concern in radiation protection. Currently, radiostrontium is of interest for evaluation of the health effects of the Chernobyl accident and for epidemiological studies in populations exposed to releases from the Mayak nuclear facilities in Russia. Ingestion is one of the most important exposure pathways involving radioactive strontium. The main sources of published data on the fraction of the ingested strontium that is transferred to plasma (f1) are summarized. For some of these studies, the original data had to be reanalyzed and a new iterative method to account for the elimination in feces of strontium of endogenous origin (i.e., that was absorbed to blood and has already been returned into feces) was employed. Data indicate no significant dependence of the absorbed fraction on sex or age at exposure within the adult group, but absorption of strontium is reduced if the intake of stable calcium is very high and is enhanced if the intake of calcium is very low. The probability distribution function of f1 values is well represented by a lognormal curve with a geometric mean of 22.3% and a geometric standard deviation of 1.44 (95% confidence interval 10.9% to 45.6%, or about a factor of 2 around the geometric mean). This distribution can be considered representative for the variability of the f1 values in a population of healthy adults.

Administration, Oral↗

Glycoproteins released into the culture medium of differentiating murine neuroblastoma cells.

C-1300 murine neuroblastoma cells release glycoproteins into the culture medium. The process was studied by prelabeling spinner cultures for 12 to 60 hours with [3H]glucosamine. Then, the medium was removed and replaced with fresh medium lacking radioactive isotope. Soluble material released into the medium during the subsequent 2-hour incubation was collected by trichloroacetic acid precipitation. The released proteins were then separated by discontinuous polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. The electrophoretograms of glycoproteins obtained from cultures labeled for different lengths of time were very similar; three major radioactive regions centered about molecular weights 87,000, 66,000, and 55,000 were present. When spinner cells were transferred to monolayer culture in the presence of N6,O2' dibutyryl adenosine 3':5'-monophosphate (Bt2cAMP), differentiation (extension of neurites twice the diameter of the perikaryon) was observed. Monolayer cultures grown in the presence of Bt2cAMP and [3H]glucosamine for 12 hours released glycoproteins which gave a gel electrophoresis pattern similar to that obtained using spinner cultures. However, after 60 hours in the presence of Bt2cAMP and [3H]glucosamine, the released radioactive material consisted almost exclusively of glycoproteins of the 66,000 molecular weight class. Similar results were obtained if [3H]fucose was substituted for [3H]glucosamine, or if bromodeoxyuridine (which also induced differentiation) was substituted for Bt2cAMP. Similar experiments using radioactive amino acids were conducted with both spinner and monolayer cultures. Much of the released radioactive material was contained in the same three molecular weight classes as the glycoproteins released by spinner cells prelabeled with [3H]glucosamine, and this pattern did not vary with length of labeling period or type of culture. These results may imply that the glycosylation of released proteins is influenced by agents which can induce differentiation. The origin of this released material is discussed. [3H]Glucosamine-labeled glycoproteins of the molecular weight class centered about 55,000 (discussed above) were isolated by preparative gel electrophoresis. They co-migrated with authentic mouse brain microtubular protein as two closely spaced bands on a number of different electrophoretic systems. This protein fraction was also characterized as complexing with a monospecific antitubulin antibody.

Bromodeoxyuridine↗

Effects of radioiodination on hormone binding ability.

This paper presents the effects of 125I labelling on human chorionic gonadotropin binding ability. The results obtained showed a marked difference in the half-life of the specific radioactivity of the radiolabelled hormone comparing the one obtained by "self-displacement" analysis and that calculated considering the half-life of the radioactive isotope (60 days for 125I). The decrease in the hormone half-life (t 1/2 = 3.10 days) was demonstrated by binding experiments performed at various days after hormone labelling. The affinity constant (Ka) and the number of binding sites obtained after Scatchard analysis using rat testes as receptor source, remained constant when the "self-displacement" specific radioactivity was used while they varied significantly if the 60 days half-life was considered for the data processing. The importance of the labelled hormone degradation as a possible cause of the decrease in the binding ability is also described.

Animals↗

[Clinical application of sentinel lymph node detection to early stage cervical cancer].

BACKGROUND & OBJECTIVE: Sentinel lymph node (SLN) identification has been increasingly used in the treatment design of a variety of solid tumors, particularly breast cancer and melanoma. A negative SLN predicts the absence of tumor metastases in the regional lymph nodes with high accuracy. This study was to investigate the clinical value of combined isotope-dye technique for detecting SLN, and to evaluate the accuracy of SLN in predicting the pelvic lymph nodes status in patients with early stage cervical cancer. METHODS: A total of 27 patients with early stage cervical cancer,scheduled for radical hysterectomy and total pelvic lymphadenectomy, were eligible for the study. Lymphoscintigraphy was performed with injection of radioactivity isotope (99m)Tc-labeled dextran ((99m)Tc-DX) into the uterine cervix 16 h before surgery. Methylthioninium (4 ml) was injected into the same points as (99m)Tc-DX during surgery, and the patients underwent lymphatic mapping with a handheld gamma-detecting probe. After resection of SLNs, standard radical hysterectomy with pelvic lymph node dissection was performed. All removed lymph nodes, including the SLNs, were examined by routine histopathology. The histopathologic results of SLNs and non-SLNs were compared. RESULTS: The detection rates of SLN were 96.3% by blue dye method, and 100% by radiolabeled tracer or combined isotope-dye. Blue dye method identified 61 SLNs, radiolabeled tracer identified 69 SLNs, and combined isotope-dye identified 70 SLNs. Preoperative SPECT/CT fusion images detected 4 SLNs in the parametrium. Seven (25.9%) patients had lymph node metastasis. The sensitivity, accuracy, negative predictive value, and false negative rate of SLN detection were 85.7% (6/7), 96.3% (26/27), 95.2% (20/21), and 14.3% (1/7), respectively. CONCLUSIONS: SPECT/CT imaging not only is superior to planar imaging in detecting SLN but also enables precise localization of SLNs. The combined isotope-dye method can improve the accuracy of SLN detection. SLN detection can accurately predict the pelvic lymph nodes status in early stage cervical cancer.

Adult↗

Dosimetric effects of edema in permanent prostate seed implants: a rigorous solution.

PURPOSE: To derive a rigorous analytic solution to the dosimetric effects of prostate edema so that its impact on the conventional pre-implant and post-implant dosimetry can be studied for any given radioactive isotope and edema characteristics. METHODS AND MATERIALS: The edema characteristics observed by Waterman et al (Int. J. Rad. Onc. Biol. Phys, 41:1069-1077; 1998) was used to model the time evolution of the prostate and the seed locations. The total dose to any part of prostate tissue from a seed implant was calculated analytically by parameterizing the dose fall-off from a radioactive seed as a single inverse power function of distance, with proper account of the edema-induced time evolution. The dosimetric impact of prostate edema was determined by comparing the dose calculated with full consideration of prostate edema to that calculated with the conventional dosimetry approach where the seed locations and the target volume are assumed to be stationary. RESULTS: A rigorous analytic solution on the relative dosimetric effects of prostate edema was obtained. This solution proved explicitly that the relative dosimetric effects of edema, as found in the previous numerical studies by Yue et. al. (Int. J. Radiat. Oncol. Biol. Phys. 43, 447-454, 1999), are independent of the size and the shape of the implant target volume and are independent of the number and the locations of the seeds implanted. It also showed that the magnitude of relative dosimetric effects is independent of the location of dose evaluation point within the edematous target volume. It implies that the relative dosimetric effects of prostate edema are universal with respect to a given isotope and edema characteristic. A set of master tables for the relative dosimetric effects of edema were obtained for a wide range of edema characteristics for both (125)I and (103)Pd prostate seed implants. CONCLUSIONS: A rigorous analytic solution of the relative dosimetric effects of prostate edema has been derived for a class of edema characterized by Waterman et al. The solution proved that the dosimetric effects caused by the edema are universal functions of edema characteristics for a given isotope. It provides an efficient tool to examine the relative dosimetric effects of edema for any given edema characteristics and for any isotopes that may be considered for prostate implants.

Brachytherapy↗

Regulation of heat-shock protein synthesis in chicken muscle culture during recovery from heat shock.

Exposure of chick myotube cultures to a temperature (45 degrees C) higher than their normal growing temperature (37 degrees C) caused extensive synthesis of three major polypeptides of Mr = 25 000, 65 000 and 81 000 referred to as 'heat-shock polypeptides' (hsps). When these cells were allowed to recover from heat-shock treatment at 37 degrees C for 6-8 h, the rate of accumulation of isotope into the 65 000-Mr and 81 000-Mr hsps declined to levels comparable to those in control cultures maintained at 37 degrees C. However, incorporation of isotope in the 25 000-Mr hsp continued at an elevated rate for a longer period than the 65 000-Mr and 81 000-Mr hsps. When heat-shocked cells were allowed to recover at 37 degrees C in the presence of actinomycin D to block new mRNA synthesis, the hsp synthesis as measured by the incorporation of radioactive isotope in these polypeptides continued at levels comparable to those in heat-shocked cells prior to recovery. The block of recovery by actinomycin D was due to the presence of a greater amount of functional hsp mRNAs in the polysomes as compared to untreated controls. The role of competition between the mRNAs for hsps and normal cellular proteins for the translation machinery in regulating protein synthesis during the recovery from heat shock has been discussed.

Animals↗

[Effects of chronic effects of lead nitrate and ionizing radiation on mutagenesis in Arabidopsis Thaliana (L.) Heynh].

Plants of Arabidopsis thaliana were grown in a laboratory conditions on the soil (black earth, chemozem) which was polluted with a radioactive isotopes of caesium, 134 + 137 Cs. Increase in specific activity of samples from 217 to 1025 and 2529 Bq/kg resulted in increase of embryonic mutation rate in Arabidopsis from 8.2 to 20.2 and 51.6% respectively. Bringing Pb2+ in a dose of 16 mg into the soil resulted in statistically significant decrease in mutation rate. Further increase of lead concentration in radioactive soils to 32, 64, 96, 128, 160 and 320 mg/kg resulted in growth of the mutation rates in the plants which were grown on the soil with "low" and "'middle" specific activity of caesium, and in decrease of the mutation rates in the plants which were grown on the soil with "high" specific radioactivity. The last process apparently was connected with the intensive growth in the number of sterile seeds in the pods.

Arabidopsis↗

[Methods of treatment of tumors of the soft parts and bones of the limbs and extremities. Analysis of case records].

218 patients examined for localized cancer of the extremities (50% benign, 50% malignant) are reported. The incidence is considered by sex and age. Demolition surgery was carried out in 35 patients and 27 locoregional treatment with antiblastics and radioactive isotopes was employed. Conservative surgery was used in 158. Operative mortality was less than 1% (2 cases out of 218) and did not reach 6% if amputations and disarticulations alone are considered. There were no deaths in cases submitted to radiochemotherapy and inguinocrural hymphadenectomy. The series includes a 15-years survival for giant-cell tumour of the femur treated with radioactive microsphores, an 11-years survival for a popliteal melanoma submitted to radiocolloid infiltration, a 9-year survival for femoral osteosarcoma for which hip disarticulation was carried out and a 4-year survival for a recurrent rhabdomyosarcoma of the hip operated by hemipelvectomy.

Adolescent↗

Duplex PCR for Autosomal Dominant Spinocerebellar Ataxia Testing: A Nonradioactive Rapid Screening Method.

Background: Current DNA diagnostic testing for spinocerebellar ataxias (SCAs) 1, 2, 3, and 6 involves four separate tests based on radioactively-labeled poly merase chain reaction (PCR). Although this approach allows accurate allele sizing, it also is time-consuming and requires manipulation with hazardous radioactive isotopes. Methods and Results: A rapid screening approach was developed based on a nonradioactive and duplexed PCR assay coupling SCA 1 and SCA 3 together and SCA 2 and SCA 6 together. This was achieved by designing new primers that amplify all normal and mutant alleles in nonoverlapping size ranges. A series of negative and positive samples previously tested with the single radioactively labeled PCRs was tested using the new duplex PCRs; 100% concordancy was achieved. Conclusion: This novel approach of nonradioactive, duplex PCRs for autosomal dominant spinocerebellar ataxias is a rapid, reliable, and cost-effective diagnostic screening approach that is suitable for laboratories with high sample load and/or laboratories seeking to reduce their use of radioisotopes.

Journal Article↗

Strong changes in lipoproteins and autoantibodies of blood serum of the Tundra Nency population as a result of environmental radiation on the territory they inhabit.

As a result of large-scale nuclear tests on the Novaya Zemlya test site (1955-62) the Tundra Nentsy population of Yamal-Nentsy autonomous region (YNAR) fell under the constant influence of incorporated radioactive isotopes (137Cs and 90Sr). Therefore, it is very important to analyze a possible spectrum of diseases of Tundra Nentsy population.

Autoantibodies↗

Radioactivity measurements on migrating birds (Turdus philomelos) captured in the Comunidad Valenciana (Spain).

The radionuclides 137Cs, 134Cs and 90Sr have been measured in edible tissues and bones of migratory birds (song-thrushes, Turdus philomelos) from central and northern Europe and captured in the Comunidad Valenciana, Spain in the 1994 autumn-winter season. Eight years after the Chernobyl accident, extensive agricultural lands in Europe are still contaminated and this study shows that there was a transfer of radioactive isotopes to the captured migratory song-thrushes. The whole-body dose commitment to humans consuming these birds is estimated.

Agriculture↗

Radiochemical analysis of 41Ca and 45Ca.

The radioactive isotopes of calcium, 41Ca (t1/2 = 1.03 x 10(5) yr) and 45Ca (t1/2 = 163 d), are produced by neutron capture in the stable isotopes 40Ca and 44Ca, respectively. These radionuclides are present in the environment due to the reactions between the galactic cosmic rays and the earth's surface, and in nuclear power plants by the activation of the structural components of nuclear reactor vessels. The aim of this paper is to propose a radiochemical separation method of 41Ca and 45Ca from the other beta gamma emitters present in radioactive materials, based on selective precipitation reactions. The activities were measured by liquid scintillation counting (LSC). The obtained decontamination factors are satisfactory for each radioactive component of the initial sample in that their activities in the final product were lower than the minimum detectable activity (MDA) due to the effectiveness of the radiochemical procedure. The sensitivity of the method allows the radiological characterization of 41Ca and 45Ca content in radioactive materials.

Beta Particles↗

Experiments with thermalized rare isotope beams from projectile fragmentation: a precision mass measurement of the superallowed beta emitter 38Ca.

The mass of the short-lived radio nuclide 38Ca (T(1/2) = 440 ms) has been measured with the 9.4-T Penning trap mass spectrometer of the Low-Energy Beam and Ion Trap Facility. A mass uncertainty of deltam = 280 eV has been achieved, corresponding to deltam/m = 8 x 10(-9). The result makes 38Ca, a superallowed beta emitter, a new candidate to test the conserved-vector-current hypothesis. The experiment is also the first demonstration that short-lived radioactive isotopes produced by projectile fragmentation of relativistic heavy-ion beams can be slowed down and prepared such that precision experiments of this kind are possible.

Journal Article↗

Radiation impact caused by activation of air from the future GSI accelerator facility fair.

The Gesellschaft für Schwerionenforschung in Darmstadt is planning a new accelerator Facility for Antiproton and Ion Research (FAIR). Two future experimental areas are regarded to be the most decisive points concerning the activation of air. One is the area for the production of antiprotons. A second crucial experimental area is the so-called Super Fragment Separator. The production of radioactive isotopes in air is calculated using the residual nuclei option of the Monte Carlo program FLUKA. The results are compared with the data for the activation of air given by Sullivan and in IAEA report 283. The resulting effective dose is calculated using a program package from the German Federal Office for Radiation Protection, the Bundesamt für Stranlenschutz. The results demonstrate that a direct emission of the total radioactivity produced into the air will probably conflict with the limits of the German Radiation Protection Ordinance. Special measures have to be planned in order to reduce the amount of radioactivity released into the air.

Air↗

The measurement of glucose turnover and oxidation using radioactive and stable isotopes.

Isotopes have become the best means for investigating glucose kinetics in vivo. With the recent greater availability of stable isotopes there has developed a need to understand how data may be obtained from the use of both radioactive and stable glucose tracers. Described for the nonexpert is the calculation of glucose appearance and disappearance, clearance and oxidation using both stable and radioactive glucose isotopes, administered both by bolus and primed constant infusion and under both steady and nonsteady state conditions. Other substrates may be studied using similar methodology. The use of stable substrate isotopes will be an expanding field of metabolic research in man.

Glucose↗