Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Radionuclide Generators”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources

Dynamic imaging of the respiratory cycle with 81mKr.

To define the regional ventilation of the human lung, subjects were monitored with a gamma camera, while breathing air labeled with radioactive 81mKr which is being continuously eluted from a generator. The information observed is displayed as a reiterated multiframe moving picture. This is accomplished by storing the information from multiple breaths, selecting acceptable cycles (determined by the duration of inspiration and expiration and the amplitude to extremes of the cycles), and normalizing the usable information and converting the summed data into sequential frames, which are repeatedly shown on a video screen from computer memory.

Computers↗

A novel four-dimensional image registration method for radionuclide therapy dosimetry.

A novel method for registering sequential SPECT scans (4DRRT) is described, whereby all sequential scans acquired in the course of a therapy or a pre-therapy tracer study may be registered in one pass. The method assumes that a monoexponential decay function can be fitted to the series of sequential SPECT scans. Multiple volumes, presenting with different decay rates, are fitted with different mono-exponential functions. The MSSE (mean sum of squared errors in the least-squares fit algorithm), over the volume used for registration, is the cost function minimized at registration. Simulated data were used to assess the effect of thresholding, smoothing, noise and the multi-exponential nature of the four-dimensional (4D) SPECT studies on the performance of 4DRRT, resulting in three-dimensional (3D) residual registration errors <3.5 mm. The 4DRRT method was then compared to the following 3D registration methods: the correlation coefficient, the sum of absolute differences, the variance of image ratios and the mutual information. The comparisons, using both simulated and clinical data, were based on the standard deviation of the effective decay time distribution, generated from the registered 4D dataset, and showed that image registration using 4DRRT is simpler and more robust compared to the 3D techniques, especially when multiple tumour sites with different decay rates are present.

Algorithms↗

Breast cancer seeking agents: basic approach.

The knowledge of biochemical and physiological mechanisms involved in tissue localization is important so as to understand the information given by diagnostic nuclear medicine imaging, and eventually to design new radiopharmaceuticals. The cellular mechanisms which permit a high cancer uptake involve the perfusion and metabolism around the tumour tissue, the interference with normal function, the altered perfusion and/or metabolism within the tumour. All these phenomena can contribute to a high concentration of particular radiotracers in cancer and can create a favourable tumour/background ratio uptake sufficient for cancer imaging. Those molecules might be also powerful tools for reaching an advanced understanding of neoplastic and even "normal" cell biology. During these last years, some radiotracer specifically designed for different applications proved to be promising radiopharmaceuticals for breast cancer imaging. This is the case of monoclonal antibodies (Mabs) developed in the past against membrane cancer antigens. Other tracers, originally proposed for the study of vascular perfusion (cardiovascular tracers), have also revealed a capacity to be taken up by cancer cells. The radiopharmaceuticals mostly used as tumour seeking agents today (Radiothallium, Sestamibi, Tetrophosmin) were generated with other applications in mind. In this paper we review the mechanisms of uptake of the most relevant agents currently proposed for breast cancer imaging, including 18F-fluorodeoxyglucose (FDG). The radiotracers will be examined on the basis of the available scientific evidence regarding their cellular uptake and release. Moreover, we report our preliminary studies on the cellular uptake and release of these and other compounds recently introduced in clinical trials.

Breast Neoplasms↗

Remediation of Hanford's N-Reactor Liquid Waste Disposal Sites.

Hanford's N-Reactor operated from 1963 to 1987 generating approximately 9 x 10 m of radioactive and hazardous liquid effluent as a result of reactor operations. Two liquid waste disposal sites, essentially large trenches designed to filter contaminants from the water as it percolates through the soil column, were established to dispose of the effluent. The discharges to the sites included cooling water from the reactor primary, spent fuel storage, and periphery systems, along with miscellaneous drainage from reactor support facilities. Today, both sites are classified as Treatment Storage and Disposal Facilities under the Resource Conservation and Recovery Act of 1976, which makes them priority sites for remediation. The two sites cover approximately 4,100 m and 9,300 m, respectively. Remediation of the sites requires removing a combined total of approximately 2.6 x 10 kg of contaminated soil and debris. Principal radionuclides contained in the soil/debris are Co, Cs, Pu, and Sr. Remediation of these waste sites requires demolishing concrete structures and excavating, hauling, and disposing of contaminated soils in work areas containing high levels of contamination and whole body dose rates in excess of 1 mSv h. The work presents unique radiological control challenges, such as minimizing external dose to workers in a constantly changing outdoor work environment, maintaining contamination control during removal of a water distribution trough filled with highly contaminated sludge, and minimizing outdoor airborne contamination during size reduction of highly contaminated pipelines. Through innovative approaches to dose reduction and contamination control, Hanford's Environmental Restoration Contractor has met the challenge, completing the first phase on schedule and with a total project exposure below the goal of 0.1 person-Sv.

Journal Article↗

GRP receptor-targeted PET of a rat pancreas carcinoma xenograft in nude mice with a 68Ga-labeled bombesin(6-14) analog.

UNLABELLED: Bombesin (BN), a 14-amino-acid peptide, shows high affinity for the human gastrin-releasing peptide receptor (GRP-r), which is overexpressed on several types of cancer, including prostate, breast, gastrointestinal, and small cell lung cancer. Thus, radiolabeled BN or BN analogs may prove to be specific tracers for diagnostic and therapeutic targeting of GRP-r-positive tumors in nuclear medicine. This study evaluated a novel BN analog labeled with the positron emitter 68Ga for receptor imaging with PET. METHODS: DOTA-PEG2-[D-Tyr6,beta-Ala11,Thi13,Nle14] BN(6-14) amide (BZH3) (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid; PEG is ethyleneglycol (2-aminoethyl)carboxymethyl ether) was synthetized using the Fmoc strategy and radiolabeled with either 67Ga or 177Lu for in vitro and biodistribution experiments. 68Ga for PET was obtained from a 68Ge/68Ga generator. In vitro binding, internalization, and efflux were determined using the pancreatic tumor cell line AR42J. Biodistribution of the peptide as a function of time and dose was studied in AR42J tumor-bearing mice. RESULTS: In vitro assays demonstrated a high affinity of 67Ga-BZH3 (dissociation constant = 0.46 nmol/L), a rapid internalization (70% of total cell-associated activity was endocytosed after a 15-min incubation), and an intracellular retention half-life (t1/2) of the 67Ga activity of 16.5 +/- 2.4 h. Biodistribution indicated a dose-dependent uptake in the tumor and a prolonged tumor residence time (t1/2 approximately 16 h). Clearance from GRP-r-negative tissues was fast, resulting in high tumor-to-tissue ratios as early as 1 h after injection. Replacing 67Ga by 177Lu, a therapeutic radionuclide, for peptide labeling resulted in a slightly reduced (approximately 20%) tumor uptake and tumor residence time of 177Lu-BZH3. In contrast, 177Lu decline in the pancreas was significantly accelerated by a factor of 3 compared with that of 67Ga. PET of mice with 68Ga-BZH3 clearly delineated tumors in the mediastinal area. CONCLUSION: The promising in vivo data of 68Ga-BZH3 indicate its potential for an improved localization of GRP-r-positive tumors and also suggest its application in patients. PET may also be favorably used for GRP-r density determination, a prerequisite for therapeutic applications.

Animals↗

A modified composite video signal generator for the gamma 11 computing system.

Many nuclear medicine departments use the Gamma 11 computing system for image processing. In many cases, clinicians would like to display or record these images on equipment that has been designed for use with standard closed-circuit television or broadcast-type composite video signals. Unfortunately, the signals provided by the Gamma 11 differ from these standard signals in a number of important ways. The circuitry presented here converts the computer's output signals into a composite waveform that will properly drive virtually all equipment designed for closed-circuit television or standard broadcast-type applications.

Computers↗

Significance of (111)In-DTPA chelate in renal radioactivity levels of (111)In-DTPA-conjugated peptides.

Metabolic studies of (111)In-DTPA-labeled polypeptides and peptides showed that the radiolabeled (poly)peptides generated (111)In-DTPA-adducts of amino acid that possess long residence times in the lysosomal compartment of the tissues where (poly)peptides accumulated. However, a recent study suggested that metal-chelate-methionine (Met) might possess in vivo behaviors different from metal-chelate adducts of other amino acids. In this study, to elucidate whether some biological characteristics of Met may accelerate the renal elimination rate of (111)In-DTPA-adduct of Met into urine, (111)In-DTPA-Met(1)-octreotide was synthesized and the renal handling of (111)In-DTPA-Met was investigated using (111)In-DTPA-L-Phe(1)-octreotide (Phe represents phenylalanine), which was reported previously, as a reference. Both (111)In-DTPA-conjugated octreotide analogs were stable against 3-h incubation in murine serum at 37 degrees C. Both (111)In-DTPA-octreotide analogs also showed rapid clearance of the radioactivity from the blood and similar accumulation of the radioactivity in the kidney. No significant differences were observed in the renal radioactivity levels from 10 min to 24 h postinjection between the two. Metabolic studies indicated that (111)In-DTPA-Met(1)-octreotide and (111)In-DTPA-L-Phe(1)-octreotide generated (111)In-DTPA-adducts of Met and Phe, respectively, as the final radiometabolites at similar rates. These findings suggested that the long residence times of the radioactivity in tissues after administration of (111)In-DTPA-labeled peptides and polypeptides would be attributed to inherent characteristics of (111)In-DTPA chelate.

Animals↗

A priori identifiability of a one-compartment model with two input functions for liver blood flow measurements.

An extended dual-input Kety-Schmidt model can be applied to positron emission tomography data for the quantification of local arterial (f(a)) and local portal-venous blood flow (f(p)) in the liver by freely diffusible tracers (e.g., [15O]H2O). We investigated the a priori identifiability of the three-parameter model (f(a), f(p) and distribution volume (Vd)) under ideal (noise-free) conditions. The results indicate that the full identifiability of the model depends on the form of the portal-venous input function (c(p)(t)), which is assumed to be a sum of m exponentials convolved with the arterial input function (c(a)(t)). When m>or=2, all three-model parameters are uniquely identifiable. For m=1 identifiability of f(p) fails if c(p)(t) coincides with tissue concentration (q(t)/Vd), which occurs if c(p)(t) is generated from an intestinal compartment with transit time Vd/f(a). Any portal input, f(p) c(p)(t), is balanced by the portal contribution, f(p) q(t)/Vd, to the liver efflux, leaving q(t) unchanged by f(p) and only f(a) and Vd are a priori uniquely identifiable. An extension to this condition of unidentifiability is obtained if we leave the assumption of a generating intestinal compartment system and allow for an arbitrary proportionality constant between c(p)(t) and q(t). In this case, only f(a) remains a priori uniquely identifiable. These findings provide important insights into the behaviour and identifiability of the model applied to the unique liver environment.

Animals↗

Beta blockers in heart failure: a comparison of a vasodilating beta blocker with metoprolol.

OBJECTIVE: To determine whether a third generation vasodilating beta blocker (celiprolol) has long term clinical advantages over metoprolol in patients with chronic heart failure. DESIGN: A double blind placebo controlled randomised trial. SETTING: University teaching Hospital. PATIENTS: 50 patients with stable chronic heart failure (NYHA class II-IV) due to idiopathic dilated, ischaemic, or hypertensive cardiomyopathy, with left ventricular ejection fraction < 0.45. INTERVENTIONS: Celiprolol 200 mg daily (n = 21), metoprolol 50 mg twice daily (n = 19), or placebo (n = 10) for three months with a four week dose titration period. After the double blind period, patients entered an open label study (with placebo group receiving beta blockers) and were assessed after one year. MAIN OUTCOME MEASURES: Clinical response, efficacy, and tolerance were assessed by the Minnesota heart failure symptom questionnaire six minute walk test, Doppler echocardiography (systolic and diastolic function), radionuclide ventriculography, and atrial and brain natriuretic peptides measured at baseline and after three months. RESULTS: In the metoprolol group at 12 weeks v baseline there was a 47% reduction in symptom score (p < 0.001), improvement of NYHA class (mean (SEM), 2.6 (0.12) to 1.9 (0.13), p = 0.001), exercise distance (1246 (54) to 1402 (52) feet, p < 0.001), and left ventricular ejection fraction (26.9(3.1)% to 31(3.0)%, p = 0.016), and a fall in heart rate (resting, 79 (3) to 62 (3) beats/min, p < 0.001). In the celiprolol group there was a 38% reduction in symptom score (p = 0.02), less improvement in exercise distance (1191 (55) to 1256 (61) feet, p = 0.05), and no significant changes in NYHA class, left ventricular ejection fraction, or heart rate. Mortality at one year was 11% in metoprolol and 19% in the celiprolol group, and symptomatic improvement was maintained in the survivors. CONCLUSIONS: Both drugs were well tolerated but the vasodilator properties of celiprolol do not seem to provide any obvious additional benefit in the long term treatment of heart failure.

Adrenergic beta-Antagonists↗

Observer performance with computer-generated images of 201Tl-Cl myocardial perfusion.

The effect of simple image processing on the interpretation of 201Tl-Cl myocardial perfusion images were evaluated by ROC analysis. Polaroid images of the cathode ray tube of an Anger camera and computer-processed transparent images recorded in color and shades of gray were examined by multiple observers. A total of 198 observer responses was accumulated for each of five image formats. The observer responses were compared with results established by coronary angiography. Better observer performance was obtained for all computer-generated images except in the region of low false positive values. The responses for color-scale formats were, in general, superior to those from the gray-scale formats. No significant improvement in observer performance resulted from the use of background subtraction with a rescaling of the 16-level gray scale to the residual information. When nine-point smoothing was applied to the color-scale display format, there was a poorer observer response.

Computers↗

Delayed cerebral hyperperfusion syndrome caused by prolonged impairment of cerebrovascular autoregulation after carotid endarterectomy: case report.

OBJECTIVE AND IMPORTANCE: Cerebral hyperperfusion syndrome is a rare but potentially devastating complication that typically occurs within several days after carotid endarterectomy. CLINICAL PRESENTATION: A 66-year-old man experienced asymptomatic cerebral hyperperfusion as demonstrated by single-photon emission computed tomography (SPECT) during a 2-week period after undergoing right carotid endarterectomy. This phenomenon occurred despite intensive pharmacological control of blood pressure. On the 28th postoperative day, repeat SPECT demonstrated resolution of hyperperfusion, and intensive blood pressure control was discontinued. INTERVENTION: Twelve hours later, the patient experienced left motor seizures with secondary generation. SPECT performed 36 hours after the onset of seizures demonstrated the reappearance of hyperperfusion. Intensive blood pressure control was reinstituted and maintained until the 36th postoperative day. On the next day, SPECT demonstrated resolution of hyperperfusion. CONCLUSION: The present case suggests that cerebral hyperperfusion syndrome may occur at later time points (e.g., 1 mo) after carotid endarterectomy. This delayed hyperperfusion syndrome may be related to prolonged impairment of cerebrovascular autoregulation.

Aged↗

Remediation of Hanford's N-reactor liquid waste disposal sites.

Hanford's N-Reactor operated from 1963 to 1987 generating approximately 9 x 10(7) m3 of radioactive and hazardous liquid effluent as a result of reactor operations. Two liquid waste disposal sites, essentially large trenches designed to filter contaminants from the water as it percolates through the soil column, were established to dispose of the effluent. The discharges to the sites included cooling water from the reactor primary, spent fuel storage, and periphery systems, along with miscellaneous drainage from reactor support facilities. Today, both sites are classified as Treatment Storage and Disposal Facilities under the Resource Conservation and Recovery Act of 1976, which makes them priority sites for remediation. The two sites cover approximately 4,100 m2 and 9,300 m2, respectively. Remediation of the sites requires removing a combined total of approximately 2.6 x 10(8) kg of contaminated soil and debris. Principal radionuclides contained in the soil/debris are 60Co, 137Cs, 239Pu, and 90Sr. Remediation of these waste sites requires demolishing concrete structures and excavating, hauling, and disposing of contaminated soils in work areas containing high levels of contamination and whole body dose rates in excess of 1 mSv h-1. The work presents unique radiological control challenges, such as minimizing external dose to workers in a constantly changing outdoor work environment, maintaining contamination control during removal of a water distribution trough filled with highly contaminated sludge, and minimizing outdoor airborne contamination during size reduction of highly contaminated pipelines. Through innovative approaches to dose reduction and contamination control, Hanford's Environmental Restoration Contractor has met the challenge, completing the first phase on schedule and with a total project exposure below the goal of 0.1 person-Sv.

Biodegradation, Environmental↗

Targeted alpha therapy in vivo: direct evidence for single cancer cell kill using 149Tb-rituximab.

This study demonstrates high-efficiency sterilisation of single cancer cells in a SCID mouse model of leukaemia using rituximab, a monoclonal antibody that targets CD20, labelled with terbium-149, an alpha-emitting radionuclide. Radio-immunotherapy with 5.5 MBq labelled antibody conjugate (1.11 GBq/mg) 2 days after an intravenous graft of 5.10(6) Daudi cells resulted in tumour-free survival for >120 days in 89% of treated animals. In contrast, all control mice (no treatment or treated with 5 or 300 micro g unlabelled rituximab) developed lymphoma disease. At the end of the study period, 28.4%+/-4% of the long-lived daughter activity remained in the body, of which 91.1% was located in bone tissue and 6.3% in the liver. A relatively high daughter radioactivity concentration was found in the spleen (12%+/-2%/g), suggesting that the killed cancer cells are mainly eliminated through the spleen. This promising preliminary in vivo study suggests that targeted alpha therapy with (149)Tb is worthy of consideration as a new-generation radio-immunotherapeutic approach.

Alpha Particles↗

Fraction of the positive 218Po and 214Pb clusters in indoor air.

The fraction of the positively charged unattached radon decay products, 218Po and 214Pb in indoor air was determined by model calculations. The results of the calculations were confirmed by measurements in a test chamber (volume: 8 m3). The fraction of both radionuclides depends on the attachment parameter (S(1)) and the neutralisation rate (nu) in room air. The total removal parameter S1 = lambda1 + v + q(f) + X = lambda1 C1f/C0 considers the attachment rate to aerosol particles (X), plate-out rate to room surfaces (q(f)) and the ventilation rate (nu) (lambda1: decay constant of 218Po). The S1-value of room can be determined by measurement of the concentration of the unattached 218Po clusters (C1f) and radon (C0). The neutralisation rate (nu) in environmental air depends mainly on the ion production rate. The influence of the relative humidity in the range 30-95% (temperature: 20 degrees C) is negligible. In addition, equal neutralisation rates for 218Po and 214Pb could be derived. In room air with ion production rates between 5 and 500 nC kg(-1) h(-1) mainly generated by the alpha emitters of radon, thoron and their short-lived decay products, the fractions for positive 218Po clusters vary between 55 and 17% and for 214Pb clusters between 53 and 14%. For a typical average concentration of radon (50 Bq m(-3)) and thoron (10 Bq m(-3)) in homes, 48% of 218Po clusters and 45% of 214Pb clusters are positively charged.

Aerosols↗

Gallium-68 labeled red cells and platelets: new agents for positron tomography.

Red cells and platelets are labeled with Ga-68 by preparing the tga-68-hydroxy-quinoline (oxide) complex and mixing the complex with the separated cellular components. The complex is prepared by first breaking the Ga-68 EDTA chelate with concentrated hydrochloric acid, adsorption of the galluim on a strong anionic ion-exchange column, and elution of the gallium activity with distilled water. Oxine is added, the oxine complex extracted into chloroform, and--following evaporation and dissolution--the solution is added to either red cells or platelets that have been centrifuged from whole blood, washed, and suspended in normal saline. After 15 min of incubation , labeling efficiencies of greater than 90% and yields of 7 mCi are obtained from 18 mCi of Ga-68 EDTA eluted from the generator. After injection of the gallium-labeled red cells in dogs, excellent blood pool images were obtained by positron tomography. The distribution corresponded to that of 11CO-labeled red cells. When labeled platelets were injected into dogs with experimentally induced intimal injury of on carotid artery, the area of injury was clearly visualized 40 min after tracer injection.

Animals↗

Molecular imaging in small animals--roles for micro-CT.

X-ray micro-CT is currently used primarily to generate 3D images of micro-architecture (and the function that can be deduced from it) and the regional distribution of administered radiopaque indicators, within intact rodent organs or biopsies from large animals and humans. Current use of X-ray micro-CT can be extended in three ways to increase the quantitative imaging of molecular transport and accumulation within such specimens. (1) By use of heavy elements, other than the usual iodine, attached to molecules of interest or to surrogates for those molecules. The accumulation of the indicator in the physiological compartments, and the transport to and from such compartments, can be quantitated from the imaged spatial distribution of these contrast agents. (2) The high spatial resolution of conventional X-ray attenuation-based CT images can be used to improve the quantitative nature of radionuclide-based tomographic images (SPECT & PET) by providing correction for attenuation of the emitted gamma rays and the accurate delineation of physiological spaces known to selectively accumulate those indicators. Similarly, other imaging modalities which also localize functions in 2D images (such as histological sections subsequently obtained from the same specimen), can provide a synergistic combination with CT-based 3D microstructure. (3) By increasing the sensitivity and specificity of X-ray CT image contrast by use of methods such as: K-edge subtraction imaging, X-ray fluorescence imaging, imaging of the various types of scattered X-ray and the consequences of the change in the speed of X-rays through different tissues, such as refraction and phase shift. These other methods of X-ray imaging can increase contrast by more than an order of magnitude over that due to conventionally-used attenuation of X-ray. To fully exploit their potentials, much development of radiopaque indicators, scanner hardware and image reconstruction and analysis software will be needed.

Animals↗

A model for hematopoietic death in man from irradiation of bone marrow during radioimmunotherapy.

There are numerous institutions worldwide performing clinical trials of radioimmunotherapy (RIT) for cancer. For RIT, an exponentially decaying radionuclide is attached by using a chelating agent to a specific monoclonal or polyclonal tumour antibody (e.g. antiferritin IgG). The major limitation to RIT is toxicity to normal tissue in organs other than the one containing the tumour (e.g. bone marrow). The focus of this manuscript is on modelling the risk (or probability) of hematopoietic death in man for exponentially decaying patterns of high-energy beta irradiation (e.g. 90Y) of bone marrow by radioimmunoglobulin injected into the blood. The analytical solutions presented are only applicable to protocols for which significant uptake of radioactivity by the bone marrow does not occur, and only for high energy beta emitters. However, the generic equation used to obtain the analytical solutions is applicable to any continuous pattern of high energy beta irradiation. A model called the "normalized dose model" was used to generate calculated values for the LD50 as a function of the effective half-time for the radioimmunoglobulin in the blood. A less complicated empirical model was used to describe the calculated values. This model is presumed to be valid for effective half-times in blood of up to about 20 days. For longer effective half-times, the LD50 can be estimated using the normalized-dose model presented. In this manuscript, we also provide a modified Weibull model that allows estimation of the risk of hematopoietic death for single or multiple injections (in one cycle) of radioimmunoglobulin, for patients with normal susceptibility to irradiation and for patients with heightened susceptibility. With the modified Weibull model, the risk of hematopoietic death depends on the level of medical treatment provided to mitigate radiation injuries.

Antibodies, Monoclonal↗

Analysis of 99mTc-pyridoxylidene-glutamate complex formation and its preparation with tin-adsorbed-resin: Sn-Resin kit method.

99mTc-Pyridoxylidene-glutamate (Tc-PG) was introduced in 1975 by Baker et al. as a cholescintigraphic agent. Nevertheless its routine use has been limited due to the autoclaving process involved. To shorten the labeling procedure, an analysis of Tc-PG complex formation using the stannous chloride method was carried out. Sn-Resin (stannous ion adsorbed onto cation exchange resin) was used for labeling a stable Tc-PG with high efficiency. A preautoclaved complex of pyridoxal and glutamate was required but the labeling procedure took only 10-15 min after the elution of 99m-TcO4- from the generator. Formation of a complex other than a 99mTc-complex of the Schiff -base ligand pyridoxylidene-glutamate is discussed. The new formulation of a Tc-PG kit (Sn-Resin) simplified the labeling method and reproducible data to that already reported by Baker was obtained in chromatographic studies. Its suitability in hospital departments has already been shown in clinical studies.

Bile↗