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Influence of pH adjustment agents on the biologic behavior of osmium-191 impurity in iridium-191m generator eluates.

The influence of four pH adjustment agents on the biologic behavior of osmium-191 (191Os) impurity in 191Os/191mIr generator eluates was studied. Extended body clearance and biodistribution studies were performed in mice. The solutions to be injected were obtained by eluting generators with a 0.9% NaCl solution at pH 1. The pH of these eluates was adjusted to 5-9 with succinate, phosphate, lysine or NaOH solution. Our results demonstrate that the biologic behavior of these generator eluates is significantly dependent on the agent used for pH adjustment. Buffering with lysine leads to the best results: (a) the mice show no adverse reaction after injection of 150 human doses and the body clearance is very rapid and (b) more than 75% I.D. at 24 hr postinjection. Preliminary calculations based on these results suggest a significant decrease in the estimated patient radiation dose when lysine buffered 191Os/191mIr generator eluates are used for radionuclide angiography.

Animals↗

Biokinetics and dosimetry for 195Au, evaluated in an animal model.

The use of the generator produced radionuclide 195mAu, half life 30 s, has become feasible for several different investigations, e.g. cardiac studies. To assess the absorbed dose from the long lived radionuclide 195Au (the daughter of 195mAu, half life 183 days), a biodistribution study of 195Au was performed in animals. Seven rabbits were injected with eluate from a 195mHg-195mAu generator and the retention and the biodistribution of the long lived gold isotope was investigated. The activity was localized mainly in the liver and the kidneys. Transforming the data to man resulted in an absorbed dose from 195Au from 1 elution (approximately 925 MBq 195mAu) of 2.2 mGy to the kidney and 1.3 mGy to the liver and an effective dose equivalent of 0.26 mSv. The total effective dose equivalent from all radionuclides in the eluate (195mAu, 195Au, 195mHg and 195Hg), was estimated to be 0.65 mSv for a single injection (925 MBq 195mAu).

Animals↗

Radionuclides and radiopharmaceuticals for single-photon emission tomography, positron emission tomography and radiotherapy in Russia.

The current status of the manufacture of radiopharmaceuticals for diagnostic and therapeutic application in Russia is discussed, consideration being given to various aspects of the production and distribution of radionuclides, radioisotope generators and kits as well as individual radiopharmaceuticals in different regions of the country. The major focus is on the recent developments in production technologies for therapeutic and single-photon emission tomography radionuclides, technetium chemistry and synthetic approaches for the labelling of compounds with short-lived positron emitters. The status of positron emission tomography and its application are considered. The major factors restricting the expansion of nuclear imaging techniques and radiotherapy in Russia are also discussed.

Humans↗

Evaluation and application of alumina-based Rb-82 generators charged with high levels of Sr-82/85.

Generator-produced Rb-82, a 75-sec positron emitter with potential for myocardial blood-flow imaging, was studied with various ion-exchange columns to evaluate the characteristics of alumina as an adsorber for the 25-day Sr-82 parent. Test columns of alumina, Bio Rex 70, and Chelex 100 were loaded with multimillicurie amounts of no-carrier-added Sr-82/Sr-85 (Sr-85 is a production contaminant). The breakthrough of Sr-82/Sr-85, and the yield of Rb-82, were determined for long-term elutions from each column with up to 4 liter of 2% NaCl solution at pH 8 to 9. The breakthrough of Sr-82/85 was 10(-6)-10(-5) from aluminal 10(-6)-10(-4) from Chelex 100 and Bio Rex 70. The effects of eluent flow rate and concentration, and of alumina volume, on the breakthrough and yield were also studied. An improved and automated Rb-82 generator was used for myocardial and brain blood-flow studies in experimental animals and in man; it was equipped with solenoid flow-control valves and five in. of lead shielding for the alumina columns, which were charged with 25-50 mCi Sr-82 (100-150 mCi Sr-85). The Rb-82 generator with alumina column provided up to 20-40 mCi of Rb-82 as often as every 5-10 min with less than 10(-5) breakthrough of Sr-82/85 over the 2- to 3-mo, useful life of the generator.

Aluminum Oxide↗

Comparison of four commercially available 81Rb-81mKr generators: quality testing using a breathing lung phantom.

Four commercially available 81Rb-81mKr generators, including their elution systems, were compared. Considerable differences in useful output between the various generators were found. When a standardized elution system was used, the differences became much less. Differences in the tubing and inaccuracy of the flow meters were found to be the major causes of the original differences. The user should be aware of a loss of output that may occur when the generator is eluted with dry air.

Humans↗

Evaluation method for krypton-81m reservoir administration systems.

Large variations have been reported in counting rates during lung ventilation studies using different 81mKr administration systems and among different patients. A method was set up to determine the activity utilization efficiency (AUE) using various administration systems. For that purpose a simple lung simulator was developed for combination with reservoir administration systems to be tested. It was found that under normal breathing conditions the AUE is 50% using a reservoir system and only 18% in the absence of a reservoir in the administration system. The measured results were confirmed by a mathematic model. The suggested simulator is suitable for use in hospitals and also enables an indirect check on the 81Rb/81mKr generator performance.

Equipment Design↗

A new type of 81Rb-81mKr generator for medical use.

A new 81Rb-81mKr generator is described. The new generator-type is suitable for ventilation and perfusion studies. By implantation of 60 keV 81Rb+-ions into Mylar or polyethylene foils, the pure 81mKr daughter can be eluted by an air-flow or by an isotonic NaCl solution.

Humans↗

Modified in vivo behaviour of 99mTc-labelled liver-spleen preparations due to 99Mo/99mTc-generator eluate impurities.

At irregular intervals, a 99mTc-labelled microcolloid for liver and spleen scintigraphy was reported to accumulate in the lungs, in the absence of any pathophysiological condition usually associated with this phenomenon. These findings were in direct contrast to the results obtained during quality control assays performed on the production batches of the kit. The authors tested the hypothesis that the presence of Al3+ ions in the generators eluate used to label the kit caused the formation of larger size aggregates. The experimental results suggest that the 99mTc-pertechnetate solution used for labelling contained far more than 40 micrograms Al3+ per ml, hence a many-fold increase of the maximum level tolerated by the pharmacopoeia. The authors advise caution when interpreting findings of pulmonary activity in the absence of clear evidence of pathological conditions that are sometimes associated with this biodistribution pattern.

Aluminum↗

A simple radioaerosol generator and delivery system for pulmonary ventilation studies.

Details of a simple radioaerosol generator and delivery system are presented. Aerosol streams of 99mTc-DTPA solution of different distributions were produced. The most useful distribution had an activity median aerodynamic diameter (AMAD) of 0.9 micron with a geometric standard deviation of 1.5. This distribution also had more than 96% of aerosol particles with aerodynamic diameter less than 2 micron. The system has been used for patient lung ventilation studies. The aerosol breathing-in period to achieve a satisfactory count rate was 1.8 +/- 0.38 min. The radioaerosol images were excellent and comparable to those obtained with 81mKr gas.

Aerosols↗

Technetium-99m 'pseudogas' for diagnostic studies in the lung.

Combustion of a flammable aerosol of 99Tcm generates an ultrafine aerosol of approximately 0.06 micron particle radius with a narrow log-normal distribution (omega g typically 1.25), close to monodisperse. Particles with this dimension do not settle out, but diffuse in a gas-like manner without aggregation. The name 'Pseudogas' has been given to this agent, to identify its unique characteristics. The technique for Pseudogas production is described and its physical properties analysed. Predicted behaviour is verified and illustrated by a clinical example. Small-airways retention of Pseudogas in normal lungs has an estimated half-time of about ten minutes, clearing to the systemic blood stream, but considerably extended regional and total times have been observed (up to 100 min) in some patients.

Aerosols↗

Technegas: a study of particle structure, size and distribution.

Technegas (TcG) was produced using a commercially available TcG generator. The structure and size distribution of TcG particles were examined by means of the following methods: (a) transmission electron microscopy (TEM), range: 1 nm-100 microns; (b) time-of-flight mass spectroscopy (MS), range: < 3 nm; (c) photon correlation spectroscopy (PCS), range: 3 nm-3 microns. The TEM images showed graphite particles (size 7-23 nm) agglomerated into larger secondary aggregates. The size of these aggregates, determined from PCS and TEM measurements, showed a log-normal distribution and typically ranged from 60 to 160 nm. No isolated particles smaller than 3 nm could be detected by MS. We conclude that TcG particles consist of technetium-99m labelled agglomerated graphite particles and have an average size of 97 nm (geometrice standard deviation (GSD): 1.55).

Particle Size↗

Parametric imaging of regional cerebral blood flow with the short-lived isotope 195mAu.

The use of the short-lived (30 s) isotope 195mAu in brain perfusion studies has been tested on 40 patients and 8 volunteers. The activity of the eluate from the 195mHg/195Au generator was high enough to give good image statistics of brain perfusion after a single bolus injection. The examinations can be repeated after 3 min giving the same quality and without significant background. The use of a low-energy photon peak at 68 keV (Au-K alpha) allows the imaging of brain perfusion in both lateral views with almost no look-through effect. With a modified height-over-area formula for the calculation of regional cerebral blood flow parametric images were obtained of high diagnostic value. The sensitivity and reproducibility of the method has been demonstrated by mental stimulation tests on eight volunteers: after optical stimulation a clear increase of blood flow could be shown in the visual cortex.

Brain↗

Environmental and health effects of the nuclear industry and nuclear weapons: a current evaluation.

The nuclear weapons industry in the U.S. comprises nine major plants, supported by a network of subcontractors and grantee institutions. Weapons development progresses at the Lawrence Livermore and Los Alamos Laboratories under the auspices of the University of California. Fissionable materials and tritium are produced at the Savannah River Plant (du Pont) or at Hanford. Reprocessing of plutonium and weapons grade uranium and manufacture of components are carried out at Rocky Flats (formerly Dow, now Rockwell Int.). Large amounts of radionuclides are generated or involved in operations at most of the nine plants. Internal reports of surveillance efforts by weapons plant personnel to monitor emissions of radioactive gases and particulates have now been released by several of the plants (in one case through litigation). Those reports document major releases of radioactive gases and particulates to the environment in the past, and continuing routine releases of some importance. Few investigations have been made of effects from these potent carcinogens in local populations. There have been several preliminary reports (Rocky Flats, Los Alamos and Savannah River) and one comprehensive report [Ambio 10: 176 (1981)]. Evidence of significantly increased rates of cancer of the more radiosensitive organs has been demonstrated. Adequate cancer registry and vital statistics data are essential for the comprehensive investigations of somatic and genetic effects which should be carried out around all nuclear installations near population centres.

Environmental Exposure↗

The imaging of myocardial perfusion with 81mKr during coronary arteriography.

The use of 81mKr was investigated for imaging myocardial perfusion during coronary arteriography using conventional catheters. When the significance of stenosis judged by arteriography is unclear, the effect on tissue perfusion can be established and the contribution to collateral flow by each artery separately evaluated. The distribution of 81mKr, due to its 13-s half-life, represents regional blood flow. In order to evaluate interventions, studies can be repeated at a low radiation risk to patients. A sterile pyrogen-free 81Rb-81Kr generator was developed. With slow infusion, inadequate mixing and streaming takes place due to laminar flow in coronary arteries. Fast intermittent 3-ml 81Kr-dextrose bolus injections convincingly eliminated streaming artefacts. Imaging was performed in 13 patients with a mobile scintillation camera and digital imaging system. Blood flow was calculated using the inert gas washout technique. There was good correlation (r = 0.91) between coronary blood flow determinations using 81mKr and 133Xe respectively. The perfusion images correlated well with the coronary angiograms. Total coronary arterial occlusions as demonstrated by arteriography were all shown as perfusion defects during rest. During atrial pacing myocardial flow was increased two-fold in normal coronary arteries and to a lesser extent in arteries with significant disease. The most critical lesion in a branch of a left coronary artery leads to a redistribution of perfusion during pacing.

Angiography↗