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PubMed2006

Radioecological characterization of a uranium mining site located in a semi-arid region in Brazil.

The work presents the radioecological characterization of the new Brazilian uranium mining and milling site located in a semi-arid region of the country. The process characterization demonstrated that in heap leach plants most of the 226Ra remains in the leached ore. Despite the potential higher availability of radium isotopes in the soils of the studied region the lack of precipitation in that area reduces the leaching/mobilization of the radionuclides. High 226Ra and 228Ra concentrations were found in manioc while 210Pb was significant in pasture. It was suggested that a range from 10(-3) to 10(-1) may conveniently encompass most of the transfer factors (TF) values for soil/plant systems (i.e. involving different cultures, different soils and natural radionuclides). Impacts due to aerial transportation of aerosols and radon generated in the mining were proved to be minimal and restricted to an area not greater than 15 km2. Finally, uranium complexation by carbonates was shown to be the main mechanism responding for the elevated radionuclide concentration in groundwater.

Brazil↗
PubMed1997

Labels of surface-seeking radionuclides in the human skeleton.

A biokinetic model of the distribution and generation of skeletal labels of 239Pu in the human body is presented. The model is based on available information on the microdistribution of transuranics elements in animals and humans. It also makes use of morphometric and histomorphometric data characterizing the human skeleton and its turnover. The model correctly describes essential features of the microdistribution established from autoradiographic analyses. Calculated concentrations of skeletal labels of 239Pu are in good agreement with measurements from a human injection case.

Animals↗
PubMed2005

Radiolabelling DOTA-peptides with 68Ga.

PURPOSE: A new field of interest is the application of 68Ga-labelled DOTA-conjugated peptides for positron emission tomography (PET). The commercially available or house-made generators require time-consuming and tedious handling of the eluate. Radiolabelling at high specific activities without further purification is not possible, while high specific activities are necessary for peptides that potentially display pharmacological side-effects. Here we present the practical aspects and the results of radiolabelling DOTA-peptides with a TiO2-based commercially available 68Ge/68Ga generator. METHODS: Reaction kinetics and parameters influencing the incorporation of the radionuclide at the highest achievable specific activity were investigated. Since high finger doses were anticipated during handling of the high beta-energy emitter 68Ga, finger dosimetric measurements were performed during radiolabelling and in vivo administration. RESULTS: Fractionated elution of the generator revealed that 80% of the radioactivity was recovered in 1 ml. Bi- and trivalent ionic contaminants that compete for the incorporation of the radionuclide were below 50 nM; thus further tedious and time-consuming purification was avoided. Radiolabelling was performed at pH 3.5-4. Plastic shielding (> or =7-mm wall thickness) around the syringe during administration effectively eliminated the positrons. In rats 68GaCl3 had slow clearance from blood, while 68Ga-EDTA was rapidly cleared via the kidneys. Uptake of 68Ga-DOTATOC in somatostatin receptor-positive tissues was high, with no significant difference between 1 and 4 h post injection. CONCLUSION: DOTA-peptides for PET imaging can be labelled with 68Ga up to specific activities of 1 GBq per nmol within 20 min, enabling the clinical application of peptides that display potential pharmacological side-effects.

Animals↗
PubMed1988

Radioimmunoguided surgery using monoclonal antibody.

The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery.

Antibodies, Monoclonal↗
PubMed1984

Quantitative analysis of seven-pinhole tomographic thallium-201 scintigrams: improved sensitivity and estimation of the extent of coronary involvement by evaluation of radiotracer uptake and clearance.

Recent studies have shown that the sensitivity of conventional thallium-201 scintigraphy can be increased by the quantitative assessment of myocardial radiotracer clearance rates in conjunction with the evaluation of radionuclide uptake. In this study, a similar analysis of tomographic scintigrams was performed to determine the feasibility and value of this approach, particularly in estimating the extent of disease and detecting three vessel coronary involvement. Seventy patients undergoing cardiac catheterization for chest pain were studied by exercise and 3 hour delayed thallium-201 scintigrams using the seven-pinhole tomographic technique. Each study was evaluated by visual inspection of the tomographic sections and quantitative analysis. The latter approach consisted of comparing circumferential profiles of the initial post-exercise radionuclide uptake and the 3 hour clearance rates generated from each of three left ventricular slices with similar profiles representing the lower 95% confidence limits derived from 15 middle-aged volunteers. An abnormality was considered present when a patient's profile fell below these limits for a 30 degrees arc, and was ascribed to disease in a particular artery when it involved that vessel's usual distribution. Among the 61 patients without apparent primary myocardial or valvular disease, the diagnostic sensitivity of thallium scintigraphy was increased from 86% (43 of 50) to 96% (48 of 50) without a change in specificity (both 9 of 11 or 82%). More importantly, the quantitative approach permitted detection of 85% (107 of 126) of significantly obstructed coronary vessels compared with 47% (59 of 126) by visual analysis (p less than 0.001), again without sacrificing specificity (85 versus 87%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

Rapid preparation of short-lived alpha particle emitting radioimmunopharmaceuticals.

Alpha emitting radionuclides are of considerable interest for targeted radioimmunotherapy. Generator supplied 213Bi emitting 8.5 MeV alpha particles with a 45.6 min half-life has been conjugated to a monoclonal antibody (HuM195-CHX-A-DTPA) for targeted therapy of leukemia in a clinical trial. The clinical dose preparation of pharmaceutical formulation by a pair of skilled radiochemists took 25 min, which corresponds, to an overall decay loss of 30% of the initial 213Bi activity eluted from the generator. In order to allow more widespread and practical clinical use of targeted 213Bi alpha particle therapy, we developed a new procedure that is simpler, more rapid and adaptable to a hospital pharmacy. The new 10 min process includes a tandem elution and labeling, and an anion exchange column purification method that can be reproducibly used.

Alpha Particles↗
PubMed1997

Structure determination of N-linked oligosaccharides engineered at the CH1 domain of humanized LL2.

Two humanized antibody mutants, hLL2HCN1 and hLL2HCN5, engineered with CH1 domain-appended carbohydrates (CHOs) were generated to facilitate site-specific conjugation of radionuclides and anti-cancer drugs to antibodies. Such site-specific conjugation may minimize the incidence of immunoreactivity perturbation as is often observed with random conjugation. Since the compositions and structures of CHOs are important in determining the chemistry, efficiency, and extent of conjugation, the sequences of the CH1-appended CHOs were determined by exoglycosidase digestions and fluorophore-assisted CHO electrophoresis (FACE). The CHO species attached at HCN1 and HCN5 sites in hLL2HCN1 and hLL2HCN5, respectively, were distinct from each other, heterogeneous, and extensively processed. All of these CHOs were core-fucosylated complex-type oligosaccharides and contained Gal (galactose) and GlcNAc (N-acetylglucosamine) residues in the outer branches. Some of the outer branches were composed of Gal alpha1-3Galbeta1-4GlcNAc structure, also known as alpha-galactosyl epitope. Most of the CHOs were sialylated. While all HCN1-CHOs were biantennary, the majority of HCN5-CHOs (>60%) were triantennary. The CH1-appended CHOs have favorable structural characteristics suitable for site-specific conjugation. For efficient conjugation of large drug complexes, hLL2HCN5 is preferable to hLL2HCN1 because the attached CHO is larger in size and more remotely positioned from the V region. The effects of the alpha-galactosyl epitope found in these CHOs on the immunological properties of the immunoconjugates as efficient cancer diagnostics and therapeutics are being studied.

Antibodies, Monoclonal↗
PubMed1986

Use of factor analysis in the evaluation of left to right cardiac shunts.

We have compared two methods of data processing for the quantitation of left-to-right cardiac shunts using first-pass radionuclide angiography. These two methods are used for curve generation in the deconvolution analysis. The standard method involves manual definition of regions of interest. A newer method--factor analysis--provides automatic curve generation and is therefore more operator-independent. Both techniques yield curves of the venous input, lung, and background. The venous input curve is deconvolved by the lung curve, and the resultant unit impulse response is fitted by the gamma variate method to quantitate the left-to-right shunt fraction. Both techniques--factor analysis and regions of interest (ROIs)--separated the shunt patients (n = 16) from the control subjects (n = 20) with a p less than 0.001. There was less interobserver variability with the curves obtained by factor analysis than with those obtained by regions of interest. The coefficient of correlation of factor analysis results with oximetry, r, was 0.90. High sensitivity and specificity, each 94%, was achieved with curves generated by factor analysis. Time vs. activity curves generated by ROIs can achieve high sensitivity and low specificity, or vice versa, depending on the cutoff level defined for separation of the left-to-right shunt patients from the control group.

Adult↗
PubMed1984

A simple separator to generate half micron aqueous particles for lung imaging.

An aerosol of a radionuclide may be used for ventilation imaging as an alternative to radioactive rare gases. For good-quality images as few particles as possible must be deposited in the trachea and bronchi, which means that no, or very few, particles should have aerodynamic diameter of more than 2 micron. We have developed a separator to modify the output of an Acorn jet nebuliser. It reduced the proportion of particles in the aerosol with aerodynamic diameters of more than 2 micron from 60% for the unmodified output of the nebuliser to only 6%; it consisted of a cylinder of perspex with two compartments containing inert spheres, either stainless steel or glass, of diameter 3 mm (the first compartment contained two layers of spheres, and the main section was packed with spheres). To examine the efficiency of the separator system for routine clinical use we compared the images produced and the deposition of the particles in the modified aerosol (using 99TcmDTPA) with the distribution of ventilation of 81Krm in eight subjects. Despite the theoretical differences between the behaviour of a gas molecule and of a particle in the respiratory tree, the images produced using the modified aerosol delivery system were as good as those produced with 81Krm in normal subjects. In abnormal subjects the images produced were only distinguished following the calculation of a penetration index.

Adult↗
PubMed1989

Fission 99Mo/99mTc Generators--a study of their quality.

Quality was controlled of seven different 99Mo/99mTc generators sold in the Federal Republic of Germany, which were all loaded with fission molybdenum. Aim of the work was to test the 99mTc eluates for their radionuclidic and radiochemical purity. Furthermore, the 99Mo content of the aluminium oxide column was measured. Determination of the elution efficiency, measurement of the pH-value of the eluate as well as a test to detect soluble aluminium in the eluate were also performed. In addition to the chemical and physical examinations, application, quality of accessories and their practicability were tested at all generators. The methods of analysis chosen were, among others, gamma spectrometry and thin-layer chromatography; the measuring methods were a site-sensitive proportional counter (measurement of the distribution of radioactivity of the chromatograms) and atomic absorption spectrometry (Al content of the eluates). The quality control of the 99mTc eluates had satisfying results. The eluates showed - with one exception - high and sufficient radionuclidic purity and very good radiochemical purity. A considerable overload of the columns with 99Mo at the time of reference was not found. The elution yields with values between 85 and 122% were in good agreement with the requirements. All eluates had pH-values between 5.0 and 6.5, and an aluminium content below 1 microgram/ml. The generators had good performance and proved generally to be a reliable source of 99mTc-pertechnetate. The application was safe and, with some exceptions, fulfilled the requirements.

Germany, West↗
PubMed1985

Factor analysis in left ventricular first-pass radionuclide angiography: value of the ventricular factor to measure ejection fraction.

Factor analysis theoretically generates the time-activity curves of the various physiological compartments, or factors, which are superimposed in a dynamic series of scintigraphic frames. An image of the spatial distribution of each of these factors is also displayed. We tested the ability of one of these, the ventricular factor, to measure the left ventricular ejection fraction (LVEF) in first-pass radionuclide angiography (FPRA). Forty-nine patients divided into three groups were studied. In a group of 32 patients, factor analysis was compared to a conventional scintigraphic method and to contrast angiography. The coefficient of correlation was similar for both techniques (r = 0.83). To test reproducibility, another group of 10 patients received two successive injections of Au-195m, three minutes apart. The reproducibility of LVEF was r = 0.78 with factor analysis and r = 0.81 with the conventional method. In a third group of seven patients, three successive injections of Au-195m were performed in the right and in the left anterior oblique projections. The reproducibility of LVEF was r = 0.71 with factor analysis. However LVEF was significantly lower in LAO than in RAO, 50 +/- 11% vs 58 +/- 17% respectively. It is concluded that factor analysis does not offer a more reliable means of calculating LVEF than a conventional method.

Factor Analysis, Statistical↗
PubMed2005

Efforts to control the errant products of a targeted in vivo generator.

Alpha-particle immunotherapy by targeted alpha-emitters or alpha-emitting isotope generators is a novel form of extraordinarily potent cancer therapy. A major impediment to the clinical use of targeted actinium-225 (225Ac) in vivo generators may be the radiotoxicity of the systemically released daughter radionuclides. The daughters, especially bismuth-213 (213Bi), tend to accumulate in the kidneys. We tested the efficacy of various pharmacologic agents and the effect of tumor burden in altering the pharmacokinetics of the 225Ac daughters to modify their renal uptake. Pharmacologic treatments in animals were started before i.v. administration of the HuM195-225Ac generator. 225Ac, francium-221 (221Fr), and 213Bi biodistributions were calculated in each animal at different time points after 225Ac generator injection. Oral metal chelation with 2,3-dimercapto-1-propanesulfonic acid (DMPS) or meso-2,3-dimercaptosuccinic acid (DMSA) caused a significant reduction (P < 0.0001) in the renal 213Bi uptake; however, DMPS was more effective than DMSA (P < 0.001). The results with DMPS were also confirmed in a monkey model. The renal 213Bi and 221Fr activities were significantly reduced by furosemide and chlorothiazide treatment (P < 0.0001). The effect on renal 213Bi activity was further enhanced by the combination of DMPS with either chlorothiazide or furosemide (P < 0.0001). Competitive antagonism by bismuth subnitrate moderately reduced the renal uptake of 213Bi. The presence of a higher target-tumor burden significantly prevented the renal 213Bi accumulation (P = 0.003), which was further reduced by DMPS treatment (P < 0.0001). Metal chelation, diuresis with furosemide or chlorothiazide, and competitive metal blockade may be used as adjuvant therapies to modify the renal accumulation of 225Ac daughters.

Actinium↗
PubMed2007

68Ga-PET radiopharmacy: A generator-based alternative to 18F-radiopharmacy.

Positron emission tomography (PET) is becoming a dominating method in the field of molecular imaging. Most commonly used radionuclides are accelerator produced 11C and 18F. An alternative method to label biomolecules is the use of metallic positron emitters; among them 68Ga is the most promising as it can be produced from a generator system consisting of an inorganic or organic matrix immobilizing the parent radionuclide 68Ge. Germanium-68 has a long half-life of 271 days which allows the production of long-lived, potentially very cost-effective generator systems. A commercial generator from Obninsk, Russia, is available which uses TiO2 as an inorganic matrix to immobilize 68Ge in the oxidation state IV+. 68Ge(IV) is chemically sufficiently different to allow efficient separation from 68Ga(III). Ga3+ is redox-inert; its coordination chemistry is dominated by its hard acid character. A variety of mono- and bifunctional chelators were developed which allow immobilization of 68Ga3+ and convenient coupling to biomolecules. Especially peptides targeting G-protein coupled receptors overexpressed on human tumour cells have been studied preclinically and in patient studies showing high and specific tumour uptake and specific localization. 68Ga-radiopharmacy may indeed be an alternative to 18F-based radiopharmacy. Freeze-dried, kit-formulated precursors along with the generator may be provided, similar to the 99Mo/99mTc-based radiopharmacy, still the mainstay of nuclear medicine.

Chelating Agents↗
PubMed1996

A quantitative study of radionuclide characteristics for radioimmunotherapy from 3D reconstructions using serial autoradiography.

PURPOSE: Using 131I-labeled monoclonal antibody (MoAb) data, assess the dosimetrical impact of labeling the same MoAb with 186Re or 90Y, under the assumption that the biodistribution of the radiolabeled MoAb in tumor relative to blood is independent of the radionuclide. METHODS AND MATERIALS: Radial radioactivity and dose-rate distributions at 1, 4, and 7 days postinjection were derived from three dimensional (3D) reconstructions of serial autoradiographs of LS174T human colon cancer xenografts in athymic nude mice treated with a single intraperitoneal administration of 300 microCi 131I-labeled MoAb 17-1A. Bone marrow dose was calculated taking into account energy deposited external to the bone marrow cavity due to the range of the beta particles. RESULTS: For 1 cm diameter tumors, uptake was mostly at the tumor surface for earlier postinjection times, but exhibited comparable activity levels from the surface to the core of the 7-day sample. The computed dose-rate distributions for 186Re and 90Y were more uniform than for 131I, but smaller fractions of the dose were deposited within the tumor volume due to the larger mean energies of 90Y and 186Re beta particles relative to those for 131I. However, when the tumor doses were normalized to the production of equivalent bone marrow doses, in the case of athymic nude mice, the tumor doses were calculated to be 15.3 Gy (131I), 14.1 Gy (186Re), and 12.0 Gy (90Y). For comparison, these calculations were extended to the case of human therapy, yielding tumor doses of 16.7 Gy (131I), 18.2 Gy (186Re), and 13.4 Gy (90Y). CONCLUSION: In the case of colon cancer xenografts where the MoAb uptake is initially concentrated at the tumor surface, we find a decreasing tumor dose per constant bone marrow dose for radionuclides of increasing mean beta energies and decreasing half-lives. However, a radionuclide with larger mean beta energy such as 90Y generates a significantly more uniform dose deposition within the tumor, especially concerning the core of the tumor, compared to 131I. For human therapy, a gamma component adds little to the tumor dose but increases dose to the marrow.

Animals↗
PubMed1996

Modeling the washoff of 90Sr and 137Cs from an experimental plot established in the vicinity of the Chernobyl reactor.

After the Chernobyl event, a large area of land was contaminated following the deposition of radionuclides. This area became a continuing source of radionuclides to natural waters and aquatic ecosystems. In 1986, an experimental plot was constructed in a contaminated area near the Chernobyl Nuclear Power Plant to study the washoff of radionuclides by surface runoff. Concentrations of 137Cs and 90Sr were measured in the top 10 cm of the soil prior to the experiments. During two separate experiments, intense artificial rainfall was applied to the plot. A washoff scenario was then prepared with site-specific information on initial soil contamination, duration and quantities of rainfall and runoff, physicochemical properties of the topsoil, and some climatological data. Modelers were asked to predict (a) the vertical distributions of the initial concentrations of 137Cs and 90Sr in various chemical forms in the topsoil, (b) concentrations of these radionuclides in various chemical forms in the runoff water during each experiment, and (c) the total amounts of these radionuclides that were washed off during each experiment. Stochastically generated local rainfall data were used in a water budget model to generate annual average runoff and infiltration rates. A vertical, one-dimensional, multiphase, multispecies transport model was then developed to simulate the movement of contaminants in the topsoil during the 160-d period between the Chernobyl event and the experiments as well as the washouts of contaminants by runoff during the experiments and during the 24-h period thereafter. The model provided very good predictions of the vertical distributions of total contaminant concentrations in the top 10 cm of the soil; however, the concentrations in individual chemical forms were not predicted as accurately. Initially, the model overpredicted the washout of contaminants for the two experiments and the 24-h period thereafter. Fraction of runoff that flows as interflow and average sediment loading in the runoff were identified as parameters responsible for the overprediction. Calibration of the interflow fraction and adjustment of the average sediment loading in runoff to a level representative of Eastern Europe considerably improved these predictions. The complete modeling approach and comparisons of model predictions with measurements and with predictions from other modelers are presented.

Cesium Radioisotopes↗
PubMed1980

Radionuclide cinepneumography: flow-volume imaging of the respiratory cycle.

A procedure is described that generates a series of images spanning an average respiratory cycle. Images are constructed from scintigraphic data with similar respiratory flow and volume characteristics so that they may be displayed in continuous-loop movie format. This technique is noninvasive and requires little patient cooperation or technologist time. It should be most useful in investigations of dynamic pulmonary function, but may be applied to any radionuclide study affected by respiratory motion.

Humans↗
PubMed1990

Selective elimination in vitro of alloresponsive T cells to human transplantation antigens by toxin or radionuclide conjugated anti-IL-2 receptor (Tac) monoclonal antibody.

The human allogeneic mixed lymphocyte reaction is the in vitro correlate of graft rejection. Cytotoxic effector cells generated during an allogeneic mixed lymphocyte reaction were previously shown to express the human p55 IL-2 receptor subunit, whereas resting cells do not express this receptor peptide. In this study, we asked whether Pseudomonas exotoxin or bismuth-212 (an alpha-particle emitting radionuclide) coupled to the anti-IL-2 receptor mAb, anti-Tac, were able to selectively eliminate alloresponsive cells generated during an allogeneic mixed lymphocyte reaction. After assembly, anti-Tac immunoconjugates retained their binding integrity, specificity, and selectivity. Deletion of alloresponsive cells was shown by the removal of alloproliferating cells as assessed by quantitating cell recovery and by measurement of thymidine incorporation into newly synthesized DNA. Both toxin and radionuclide immunoconjugates eliminated established cytotoxic effector cells generated in an allogeneic mixed lymphocyte reaction, while leaving intact the PHA-inducible mitogenic response of the nonactivated cells. The addition of excess anti-Tac blocked all of the effects of these cytotoxic reagents. The therapeutic reagents in vitro were most effective when added just prior to the peak of the alloproliferative response, when receptor expression would be close to maximum. Thus, anti-Tac conjugated either with toxin or radionuclide is effective in vitro in specifically eliminating cytotoxic effector cells.

ADP Ribose Transferases↗
PubMed1981

Use of the radionuclide washout test in evaluation of suspected upper urinary tract obstruction.

The use of the computerized quantitative renal scan associated with the standard renogram obtained during furosemide-induced diuresis provides useful information in the assessment of suspected upper tract obstruction. With the use of 99mtechnetium diethylenetriaminepentaacetic acid or 131iodine hippuran quantitative renal scans were obtained and renograms were generated before and after intravenous furosemide injection. Rapidity of diuretic-induced radionuclide washout, as well as determination of glomerular filtration rate or effective renal plasma flow on the affected side, provides objective information with regard to renal parenchymal loss as well as upper tract emptying. We herein report our experience with 19 such patients. The radionuclide washout test is obtained easily, informative and may replace more invasive diagnostic measures.

Child↗