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Nuclear energy: health impact of carbon-14.

Estimates are presented on the carbon-14 generation rates in several reactor types and in peaceful nuclear explosions. If the carbon-14 generated in light water reactors is released, the population radiation dose rate it causes initially will be comparable to that resulting from the krypton-85 and tritium generated in these reactors. Because of the long half-life, the radiation dose commitment and the dose rate resulting from the environmental build-up of carbon-14 are considerably larger than those of the two other radionuclides.

Air Pollution, Radioactive↗

Simulation of nuclear decay

The present article depicts a software module to prepare the particles and quanta emitted during the disintegration of nuclides with complex decay schemes. This program is particularly useful for Monte Carlo simulations involving detectors showing pulse-summation effects. It generates the decay-scheme dependant input to trace the interactions of the emitted particles (and the secondary particles created) with a particular detector; then the simulation code produces emission and energy-deposition spectra for the chosen radionuclides.

Journal Article↗

Renal tubulointerstitial changes after internal irradiation with alpha-particle-emitting actinium daughters.

The effect of external gamma irradiation on the kidneys is well described. However, the mechanisms of radiation nephropathy as a consequence of targeted radionuclide therapies are poorly understood. The functional and morphologic changes were studied chronologically (from 10 to 40 wk) in mouse kidneys after injection with an actinium-225 (225Ac) nanogenerator, a molecular-sized, antibody-targeted, in vivo generator of alpha-particle-emitting elements. Renal irradiation from free, radioactive daughters of 225Ac led to time-dependent reduction in renal function manifesting as increase in blood urea nitrogen. The histopathologic changes corresponded with the decline in renal function. Glomerular, tubular, and endothelial cell nuclear pleomorphism and focal tubular cell injury, lysis, and karyorrhexis were observed as early as 10 wk. Progressive thinning of the cortex as a result of widespread tubulolysis, collapsed tubules, glomerular crowding, decrease in glomerular cellularity, interstitial inflammation, and an elevated juxtaglomerular cell count were noted at 20 to 30 wk after treatment. By 35 to 40 wk, regeneration of simplified tubules with tubular atrophy and loss with focal, mild interstitial fibrosis had occurred. A lower juxtaglomerular cell count with focal cytoplasmic vacuolization, suggesting increased degranulation, was also observed in this period. A focal increase in tubular and interstitial cell TGF-beta1 expression starting at 20 wk, peaking at 25 wk, and later declining in intensity with mild increase in the extracellular matrix deposition was noticed. These findings suggest that internally delivered alpha-particle irradiation-induced loss of tubular epithelial cells triggers a chain of adaptive changes that result in progressive renal parenchymal damage accompanied by a loss of renal function. These findings are dissimilar to those seen after gamma or beta irradiation of kidneys.

Actinium↗

Benign thyroid nodule with normal iodide trap and defective organification.

Cold thyroid nodules are generally due to impaired iodide uptake, while organification remains normal. In a case of a nodule appearing hot one hour after Tc99 m and cold 24 h after 131I-iodide, in vivo investigations showed that the trapping function was unimpaired and that the defect lay in organification. An early thyroid scan taken with 131I-iodide showed definite radioactivity in the nodule which was dischargeable by K perchlorate. This finding was confirmed by in vitro study of the tissue. Indirect evidence suggests that a defect was present in the H2O2 generating system rather than in peroxidase.

Adult↗

Characterization of the dust/smoke aerosol that settled east of the World Trade Center (WTC) in lower Manhattan after the collapse of the WTC 11 September 2001.

The explosion and collapse of the World Trade Center (WTC) was a catastrophic event that produced an aerosol plume impacting many workers, residents, and commuters during the first few days after 11 September 2001. Three bulk samples of the total settled dust and smoke were collected at weather-protected locations east of the WTC on 16 and 17 September 2001; these samples are representative of the generated material that settled immediately after the explosion and fire and the concurrent collapse of the two structures. We analyzed each sample, not differentiated by particle size, for inorganic and organic composition. In the inorganic analyses, we identified metals, radionuclides, ionic species, asbestos, and inorganic species. In the organic analyses, we identified polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, pesticides, phthalate esters, brominated diphenyl ethers, and other hydrocarbons. Each sample had a basic pH. Asbestos levels ranged from 0.8% to 3.0% of the mass, the PAHs were > 0.1% of the mass, and lead ranged from 101 to 625 microg/g. The content and distribution of material was indicative of a complex mixture of building debris and combustion products in the resulting plume. These three samples were composed primarily of construction materials, soot, paint (leaded and unleaded), and glass fibers (mineral wool and fiberglass). Levels of hydrocarbons indicated unburned or partially burned jet fuel, plastic, cellulose, and other materials that were ignited by the fire. In morphologic analyses we found that a majority of the mass was fibrous and composed of many types of fibers (e.g., mineral wool, fiberglass, asbestos, wood, paper, and cotton). The particles were separated into size classifications by gravimetric and aerodynamic methods. Material < 2.5 microm in aerodynamic diameter was 0.88-1.98% of the total mass. The largest mass concentrations were > 53 microm in diameter. The results obtained from these samples can be used to understand the contact and types of exposures to this unprecedented complex mixture experienced by the surviving residents, commuters, and rescue workers directly affected by the plume from 11 to 12 September and the evaluations of any acute or long-term health effects from resuspendable dust and smoke to the residents, commuters, and local workers, as well as from the materials released after 11 September until the fires were extinguished. Further, these results support the need to have the interior of residences, buildings, and their respective HVAC systems professionally cleaned to reduce long-term residential risks before rehabitation.

Aerosols↗

Myocardial perfusion imaging with a combined x-ray CT and SPECT system.

UNLABELLED: We evaluated a novel combined x-ray CT and SPECT medical imaging system for quantitative in vivo measurements of 99mTc-sestamibi uptake in an animal model of myocardial perfusion. METHODS: Correlated emission-transmission myocardial images were obtained from 7- to 10-kg pigs. The x-ray CT image was used to generate an object-specific attenuation map that was incorporated into an iterative ML-EM algorithm for reconstruction and attenuation correction of the coregistered SPECT images. The pixel intensities in the SPECT images were calibrated in units of radionuclide concentrations (MBq/g), then compared against in vitro 99mTc activity concentration measured from the excised myocardium. In addition, the coregistered x-ray CT image was used to determine anatomical boundaries for quantitation of myocardial regions with low perfusion. RESULTS: The accuracy of the quantitative measurement of in vivo activity concentration in the porcine myocardium was improved by object-specific attenuation correction. However, an additional correction for partial volume errors was required to retrieve the true activity concentration from the reconstructed SPECT images. CONCLUSION: Accurate absolute SPECT quantitation required object-specific correction for attenuation and partial volume effects. Additional anatomical information from the x-ray CT image was helpful in defining regions of interest for quantitation of the SPECT images.

Algorithms↗

Bismuth-212-labeled anti-Tac monoclonal antibody: alpha-particle-emitting radionuclides as modalities for radioimmunotherapy.

Anti-Tac, a monoclonal antibody directed to the human interleukin 2 (IL-2) receptor, has been successfully conjugated to the alpha-particle-emitting radionuclide bismuth-212 by use of a bifunctional ligand, the isobutylcarboxycarbonic anhydride of diethylenetriaminepentaacetic acid. The physical properties of 212Bi are appropriate for radioimmunotherapy in that it has a short half-life, deposits its high energy over a short distance, and can be obtained in large quantities from a radium generator. Antibody specific activities of 1-40 microCi/microgram (1 Ci = 37 GBq) were achieved. Specificity of the 212Bi-labeled anti-Tac was demonstrated for the IL-2 receptor-positive adult T-cell leukemia line HUT-102B2 by protein synthesis inhibition and clonogenic assays. Activity levels of 0.5 microCi or the equivalent of 12 rad/ml of alpha radiation targeted by anti-Tac eliminated greater than 98% the proliferative capabilities of HUT-102B2 cells with more modest effects on IL-2 receptor-negative cell lines. Specific cytotoxicity was blocked by excess unlabeled anti-Tac but not by human IgG. In addition, an irrelevant control monoclonal antibody of the same isotype labeled with 212Bi was unable to target alpha radiation to cell lines. Therefore, 212Bi-labeled anti-Tac is a potentially effective and specific immunocytotoxic reagent for the elimination of IL-2 receptor-positive cells. These experiments thus provide the scientific basis for use of alpha-particle-emitting radionuclides in immunotherapy.

Antibodies, Monoclonal↗

A quantitative method for the detection and localization of quantum-limited events from radionuclides in cells and tissue sections by computer-enhanced video microscopy.

Cellular dynamics often involve extremely low concentrations of biologically active substances, which can be radiolabeled and detected, localized and quantitated by autoradiography. The latter may require exposures from a few days to many months. The objective of this research was to demonstrate the feasibility of reducing this long period of data collection by one to two orders of magnitude, while maintaining or improving the spatial resolution and localization in tissues and the quantitative characteristics inherent in autoradiography. A mathematical model describing the complete system was generated using energy partition calculations to estimate photon production via scintillant per H3 beta particle emission and to estimate the subsequent photon capture based upon imaging system parameters and microscope geometry. Calculations showed that, typically, a single tritium beta particle produces a maximum of 5.8 X 10(3) photons. A photon-limited camera and microscope imaging system were selected and optimized in conjunction with a specially developed physical scintillation model. Results showed that the number of detected photoevents increases monotonically with both signal integration time and, independently, with the concentration of the radionuclide. Consequently, this work demonstrates that video microscopy imaging methods can spatially and temporally quantify very low concentrations of radiolabeled substances and can reduce data acquisition times.

Beta Particles↗

Radionuclide methodology for the assessment of the microcirculation in island pedicle flaps in a sheep model.

Island pedicle flaps with a proximal well-perfused part and a distal poorly-perfused part were raised in eight anaesthetized sheep. Autologous red blood cells were labelled in vitro with 99TcmO4 and plasma with 111In chloride. The labelled cells and plasma were injected intraarterially and both dynamic and static images of the time-course of radioactivity were obtained with a gamma camera. Time activity curves were generated for selected regions of interest of the flap. For both plasma and red cells there was a substantial decline in the amount of tracer reaching the distal part of the flap; the time to maximum counts increased and the time activity curves indicated a minor uptake and almost no clearance pattern. In general there were marked local differences in the flow of plasma and red cells. The flow of plasma was more rapid than that of the red cells in five of the eight sheep. The model provides a standardized pedicle flap having a proximal part with adequate circulation and a distal part with inadequate circulation. It is concluded that this sheep model is suitable for radionuclide studies examining those factors that influence the distribution of blood flow within this tissue.

Animals↗

Altering pharmacokinetics of radiolabeled antibodies by the interposition of metabolizable linkages. Metabolizable linkers and pharmacokinetics of monoclonal antibodies.

Monoclonal antibodies, their fragments and low molecular weight oncophilic molecules such as synthetic somatostatin derivatives have been used to deliver radioactivity to target cells for both diagnostic and therapeutic purposes. Clinical studies demonstrated high abilities of the radiolabeled antibodies and peptides for nuclear medicine applications. However, high and persistent localization of radioactivity was observed in the liver or kidney especially when these molecules are labeled with metallic radionuclides, which reduce diagnostic accuracy and compromise therapeutic effectiveness. Thus, radiolabeled antibodies and peptides would become much more useful in both targeted imaging and radiotherapy if the undesirable radioactivity localization can be diminished. As a means to reduce the undesirable radioactivity, interposition of a metabolizable linkage between an antibody and a radiolabel was proposed to generate radiolabeled small molecules of urinary excretion from the parental antibody by enzymatic cleavage of the linkage. In this paper, after indicating the rationale behind the radiopharmaceutical design, a significant role played by the interposition of the metabolizable linkage in altering pharmacokinetics of radiolabeled antibodies is described from a variety of studies so far reported with an emphasis being laid on the importance of radiometabolite-based design of metabolizable linkages.

Antibodies, Monoclonal↗

Manometric and radionuclide assessment of pharyngeal emptying before and after cricopharyngeal myotomy in patients with oculopharyngeal muscular dystrophy.

Fifteen patients with oculopharyngeal muscular dystrophy underwent cricopharyngeal myotomy for palliation of dysphagia. The aim of this work was to assess the effectiveness of this operation by using a radionuclide pharyngeal emptying study as a new quantitative method in addition to clinical and manometric evaluation. Radionuclide study was performed with the patient in both the upright and the supine positions after ingestion of 15 ml of water labeled with sulfur colloid 99mTc. Computerized data were acquired at 0.5 second intervals for 15 minutes and a pharyngeal time-activity curve was generated. Four quantitative parameters were evaluated: the time for pharyngeal clearance of 25%, 50%, and 75% of the ingested radioactive water and the pharyngeal stasis at 15 minutes. Manometric studies were also performed before and after cricopharyngeal myotomy. The pharyngeal clearance of 25%, 50%, and 75% of the water and pharyngeal stasis at 15 minutes were all improved by cricopharyngeal myotomy, decreasing from 1.2 to 0.9 second (p less than 0.04), 4.2 to 2 seconds (p less than 0.005), 15 to 7 seconds (p less than 0.02), and 10.3% to 6% (p less than 0.01), respectively. Both pharyngoesophageal and tracheobronchial symptoms were also significantly improved by cricopharyngeal myotomy. Manometric evaluation showed a decrease of the upper esophageal sphincter closing pressure from 60.1 mm Hg before to 28.2 mm Hg after the operation (p less than 0.001), and the resting pressure decreased from 34.4 to 15.7 mm Hg (p less than 0.0005). Cricopharyngeal myotomy significantly improves both symptoms and pharyngeal emptying in patients with oculopharyngeal muscular dystrophy.

Aged↗

The inhibitory effect of (111)In-DTPA(0)-octreotide on intrahepatic tumor growth after partial hepatectomy.

UNLABELLED: The aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with (111)In-diethylenetriaminepentaacetic acid (DTPA)(0)-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). METHODS: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 micro g/kg subcutaneously twice daily or with 370 MBq (111)In-DTPA(0)-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of (111)In-DTPA(0)-octreotide therapy on liver regeneration after PHx. RESULTS: PHx induced an increase in tumor growth in all experiments (P < 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. (111)In-DTPA(0)-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P < 0.01). (111)In-DTPA(0)-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, (111)In-DTPA(0)-octreotide therapy did not influence liver regeneration or liver function after PHx. CONCLUSION: Peptide receptor radionuclide therapy with (111)In-DTPA(0)-octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.

Animals↗

Validation of SPECT equilibrium radionuclide angiographic right ventricular parameters by cardiac magnetic resonance imaging.

BACKGROUND: Recent advances in the treatment of primary pulmonary hypertension (PPH), and in surgery to correct tetralogy of Fallot (TOF), have rekindled interest in evaluating right ventricular (RV) volume and ejection fraction (EF). The purpose of this investigation was to determine the accuracy of RV functional parameters assessed by single photon emission computed tomography (SPECT) equilibrium radionuclide angiography (ERNA). METHODS AND RESULTS: Twenty-eight patients with PPH (n = 15) or TOF (n = 13) (aged 28 +/- 14 years; 57% male) were analyzed by means of SPECT ERNA algorithms that automatically identified mid-RV tomographic planes, generated regions isolating the right ventricle from other structures, and presented RV-segmented regions as a cinematic display. RV EF and volumes were computed and compared with values obtained by magnetic resonance imaging (MRI). Mean values were not different between SPECT ERNA and MRI for RV EF, end-diastolic volume, and end-systolic volume (42% +/- 11% vs 41% +/- 10%, 135 +/- 67 mL vs 139 +/- 91 mL, and 87 +/- 54 mL vs 85 +/- 61 mL, respectively; P = not significant for all comparisons). Significant linear correlation (P <.0001) was found between SPECT ERNA and MRI for RV EF, end-diastolic volume, and end-systolic volume (r = 0.85, r = 0.94, and r = 0.93, respectively). No statistically significant trends or biases for RV EF were found. Intraobserver and interobserver comparisons demonstrated good reproducibility. As expected, RV volume was significantly higher and RV EF was significantly lower for patients with PPH and TOF than were values for individuals at low likelihood for coronary artery disease or other cardiac disease. CONCLUSIONS: SPECT ERNA provides accurate, reproducible assessment of RV volumes and EF and should prove useful in evaluating the magnitude of RV dysfunction in patients and in providing an objective means with which to assess the results of therapeutic interventions.

Adolescent↗

Effects of standard mitral valve replacement on left ventricular function.

Recent studies have suggested that excision of the mitral valve apparatus during mitral valve replacement impairs left ventricular performance. However, functional measurements in humans have been difficult to obtain in a load-independent fashion. To investigate this concept, 12 patients (mean age, 65 +/- 8 years; mean New York Heart Association functional class, 3.3 +/- 0.7) with 4+ mitral regurgitation (n = 8) or mitral stenosis (valve area, 1.2 +/- 0.2 cm2) (n = 4) underwent prosthetic valve replacement using crystalloid cardioplegia. No patient required therapeutic inotropic support, every patient had at least the anterior mitral leaflet excised, and paced heart rate was maintained constant throughout. Left ventricular volume was measured with radionuclide angiocardiography, left ventricular pressure with a 3F micromanometer, and left ventricular wall volume with two-dimensional transesophageal echocardiography. Left ventricular preload was varied over a mean end-diastolic pressure range of 9 to 20 mm Hg and an end-diastolic volume range of 134 to 170 mL to generate four to five steady-state pressure-volume loops before and ten minutes after cardiopulmonary bypass. Left ventricular performance was estimated with the stroke work/end-diastolic volume relationship, which is insensitive to load. After bypass, no significant change (p greater than 0.1) was noted in wall volume for patients with mitral regurgitation or mitral stenosis (175 +/- 68 to 189 +/- 63 mL/m2 and 130 +/- 22 to 127 +/- 19 mL/m2, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Measurement of gastric emptying by magnetic resonance imaging in humans.

A new noninvasive radiation-free method to measure gastric emptying in humans was developed. The upper abdomen was recorded with a magnetic resonance imager after administration of a liquid meal containing Gadolinium tetraazacyclododecane tetraacetic acid as a magnetic resonance image (MRI) marker. Meal volumes, total gastric volumes, and secretory rates were measured. The MRI technique was validated simultaneously by the double indicator method in 5 healthy volunteers and in 5 patients with symptoms of disordered gastric emptying applying gamma camera scintigraphy and MRI in randomized order. Similar gastric meal emptying curves were obtained in volunteers and in patients by MRI and the reference methods as assessed by linear (r greater than 0.90; P less than 0.001) and intraclass correlation analysis (r greater than 0.905) for T1/2, areas under the curve, and percent of gastric meal retained. Furthermore, similar total gastric volumes and gastric secretory rates were measured by MRI and the double indicator technique. The new MRI method correctly reflected gastric emptying disorders in patients. Thus for the first time it is possible to combine these measurements of gastric functions in a single method and to relate them to gastric morphology visualized by the generation of three-dimensional images.

Adult↗

Conceptual graphs as an operational model for descriptive findings.

Clinical findings are often based on impression and expressed by verbal descriptions. For their structured documentation a coherent and consistent representation model is demanding. The proposed approach is an attempt to take conceptual graphs as a formal notation for findings. Conceptual graphs are finite, connected, and bipartite graphs consisting of concept nodes that are linked by conceptual relation nodes. Concepts are organized in a type hierarchy. A subclass of conceptual graphs, called conceptual finding graphs, will be introduced that capture descriptive findings with well-defined characteristics. It will be shown, how conceptual finding graphs can serve as a coherent and consistent basis for data acquisition, database storage, and verbalization of descriptive findings. The data entry of findings can be supported by the definition of selectional constraints for conceptual relations. Database storage can be achieved by mapping conceptual finding graphs into a relational database schema. Findings can be verbalized by a text generator which takes conceptual finding graphs as input and produces morpho-syntactic surface structures. The model has been applied to an interactive report generator for bone scan studies. It provides the user with a controlled reporting vocabulary on an adaptive graphical interface, and allows the assembling of complex findings by term selection and combination based on selectional constraints. The entered findings can be stored without loss of structure. A text generation produces acceptable German reports.

Artificial Intelligence↗

Hepatic perfusion changes in patients with cirrhosis indices of hepatic arterial blood flow.

PURPOSE: This study used radionuclide angiography to evaluate semiquantitatively the hepatic arterial blood flow changes associated with cirrhosis. METHODS: The parameters of net arterial hepatic perfusion were estimated by analysis of first-pass flow studies in 11 control participants and in 15 patients with cirrhosis (Child-Pugh classification B-C). Hepatic, renal, and splenic time-activity curves were generated, normalized per pixel, and corrected for background. The rate of hepatic arterial blood flow was compared with the reference kidney and spleen perfusion using the hepatorenal and hepatolienal perfusion indices, respectively. These indices were defined as: PI = area under hepatic curve limited by time of the renal (splenic) curve peak/area under renal (splenic) curve to its peak RESULTS: The values of both these perfusion indices are significantly greater in the patients with cirrhosis than in controls (hepatorenal perfusion index, P < 0.01; hepatolienal perfusion index, P < 0.05). The values of the hepatic perfusion index (the ratio of the arterial to the total liver blood flow), which were also calculated, were elevated in the patients with cirrhosis (P < 0.01). CONCLUSIONS: The results confirm that the net hepatic arterial blood flow is increased in patients with cirrhosis. Radionuclide angiography accompanied by calculation of arterial perfusion indices may provide semiquantitative parameters of net hepatic arterial blood flow.

Hepatic Artery↗