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PubMed1986

A reproducible radionuclide procedure for measurement of cerebrospinal fluid shunt flow.

A radionuclide technique was developed to obtain reproducible measurements of cerebrospinal fluid flow in Rickham-Holter type shunt systems. In attempting to reproduce previously described radionuclide procedures, we found that different flow rate measurements can be obtained simply by changing the radiotracer injection technique or the method of analysis of the time activity curves which are generated. The importance of these technical pitfalls cannot be over-emphasized, since there is no gold standard to evaluate cerebrospinal fluid flow in vivo. An experimental model with a calibrated Harvard pump and a shunt system filled with normal saline was constructed. Aliquots of 500 microCi of pertechnetate in 0.05 ml of saline were injected serially into the center of Rickham reservoir using a size 28 needle. Time-activity curves were obtained after waiting five min to reach equilibrium, and standard curves of radiotracer clearance vs actual flow for each system used clinically in our institution were generated. In addition, a technique to quantify and thus correct for the small but significant leak of radiotracer which occurs at the site of injection in the reservoir is described. Excellent correlation was obtained between our results and the clinical and radiological findings in a preliminary clinical evaluation.

Cerebrospinal Fluid↗
PubMed1978

Assessment of radionuclide angiocardiograms using color/time images.

Color images obtained directly from the CRT display of a digital computer were used to assess the passage of radionuclides through the heart. Following separation of the right and left heart images, the former was recorded as blue and the latter as red, after which a composite image of the entire heart was generated. A cardiac chamber or greater vessel may be filled during both color/time phases if an intracardiac shunt is present. On the composite image, these overlapping areas appear as either the complementary color or white.

Child↗
PubMed1998

Prediction of prognosis in peripheral facial nerve paralysis using submandibular gland scintigraphy.

UNLABELLED: In this study, we evaluated the ability of submandibular gland scintigraphy to predict the prognosis of peripheral facial nerve paralysis. METHODS: Submandibular gland scintigraphy was performed in 78 patients with acute peripheral facial nerve paralysis. After injection of 180-370 MBq [99mTc]pertechnetate, serial 1-min images were acquired for 25 min. At 15 min after injection of radionuclide, ascorbic acid was administered intraorally to stimulate salivary secretion. Regions of interest were set manually on both submandibular glands, and time-activity curves were generated. The ratios of peak count density (PCR) and washout (WR) of the affected side to the normal side were calculated. Parameters of > or = 0.8 suggested normal affected submandibular function and indicated a good prognosis. RESULTS: Complete recovery of facial nerve paralysis was observed in 52 of 78 patients. The sensitivity, specificity and accuracy of PCR for a good prognosis were 79%, 50% and 69%, and those of WR were 85%, 77% and 82%, respectively. Positive and negative predictive values for a good prognosis were 76% and 54% in PCR and 88% and 71% in WR, respectively. When WR obtained within 14 days of the onset was used, positive and negative predictive values for a good prognosis were 94% and 73%, respectively. None of the eight patients who had values of <0.8 for both parameters within 14 days of the onset recovered completely. CONCLUSION: Submandibular gland scintigraphy can serve as a reliable indicator to predict the prognosis of acute peripheral facial nerve paralysis in its early symptomatic period.

Acute Disease↗
PubMed1986

Reversed-phase HPLC of 99mTc methylene diphosphonate bone imaging kits with quantification of pertechnetate.

Ion-pairing reversed-phase HPLC is used to separate a mixture of 99mTc methylene diphosphonate (MDP) complexes prepared by tin reduction of pertechnetate in the presence of ligand. Chromatographic conditions allow for the quantification of total pertechnetate concentration, as well as the determination of chemical purity of generator eluents from which 99mTc is derived. Both determinations can be made prior to actual labeling. Commercially available MDP kits from three manufacturers are evaluated. All three MDP kits, when labeled with 99mTc, produce multiple, chromatographically separable components. The formation of these Tc-MDP complexes is time dependent. The labeling procedure produces several products within the first 20 min, with up to fifteen complexes observed after 4 h. The results of this work demonstrate the presence of substantial chemical contamination in generator eluents.

Bone and Bones↗
PubMed1992

Calcium antagonists protect mice against lethal doses of ionizing radiation.

Currently available radioprotectors are poorly tolerated in man and the general use of aminothiol radioprotectors is compromised by their side-effects. In a search for less toxic radioprotective agents, diltiazem, a calcium antagonist with a benzothiazepine structure, was found to protect mice against a lethal (LD100) gamma radiation dose allowing survival of up to 93%. Dihydropyridine calcium antagonists such as nifedipine, nimodipine, isradipine and nitrendipine also provided radioprotection. Calcium antagonists might attenuate radiation-induced injury by inhibiting cellular calcium overload, subsequent to cell membrane damage caused by radiation-generated free radicals. In view of their good tolerance, calcium antagonists may be applied safely in situations of radiation exposure, including radiotherapy and internal radionuclide contamination. These calcium antagonists may also be viewed in other contexts where free radicals are implicated in pathological processes.

Animals↗
PubMedDate not supplied

[Use of radionuclides in therapy].

INTRODUCTION: In nuclear medicine therapy is based on deposition of certain doses of ionizing radiation in tumors or organ tissues. Regarding their linear energy transfer (LET) values and relative biological effectiveness (RBE), principal radiotherapeuticals are alpha-, beta-, beta/gamma- or electron-emitters. In principle, to achieve the desired therapeutic effect, a particular radionuclide should exhibit adequate physical, chemical and biological properties. However, considerable efforts are required in selecting an optimal radionuclide for a specific application and then, in the development of methods for its routine production. THERAPEUTIC USE OF RADIONUCLIDES: The paper reviews several aspects of use, properties and production of unsealed radiation sources which are intended to be administered for therapeutic purposes. It covers scientific and practical criteria involved in selecting the radionuclide from medical point of view. The main indications for use of radiotherapeuticals are in oncology and rheumathology. Besides well known, like 32P, 89Sr, 90Y and 131I, several other radionuclides are also listed. Some of them are already in routine use while the others are still under investigation. The main chemical forms of radionuclides and indications are revealed. Particular emphasis is put on the discussion on criteria which a radionuclide should fulfill regarding its physical properties (type, energy, half life, ratio and abundance of the particulate and gamma ray emission). Ideally, they should, together with chemical and biological properties, match with the in-vivo pharmacokinetics and localization of the radionuclide and/or radiopharmaceutical. The trend in modern nuclear medicine is introduction of radionuclides of very specific properties. This, on the other side, opens a question of their availability on the routine basis and at reasonable prices. This matter is also discussed in the present review. CONCLUSION: Production of radionuclides for therapeutic purposes (as well as those for diagnostics) is performed either in nuclear reactors or in cyclotrons. Advantages and disadvantages of each production are discussed. The main nuclear reactions for routine production of 32P, 89Sr, 90Y and 131I are given, as well as for production of several other reactor or cyclotron-produced radionuclides. These are, e.g., reactor-produced beta-emitter 169Er, beta/gamma emitters 67Cu, 153Sm, 165Dy, 186Re and electron-emitters 80mBr and 125I. Generators for production of alpha emitters 212Bi and 213Bi are also under development. It can be concluded that, at present, besides 131I, large activities of 32P, 89Sr and 90Y are available on regular basis. For many others, routine availability remains yet to be established.

Humans↗
PubMed2005

Current status of therapy of solid tumors.

The recent approval of 2 radiolabeled antibodies against cluster designation 20-positive lymphoma has led to a resurgence of interest in radioimmunotherapy. As was the case with chemotherapy development, progress has been most marked in the hematologic neoplasms, both in myeloablative and in nonmyeloablative therapeutic strategies. Success in the radioimmunotherapy of solid tumors has lagged because of the immunogenicity of murine proteins and the relatively slow clearance of humanized intact immunoglobulins. Genetic engineering has enabled the development of a variety of antigen-binding constructs of various sizes and immunobiologic characteristics. Developments in radiochemistry as well as production of an increasing number of radionuclides with therapeutic potential or optimal imaging characteristics have spurred tailored therapeutic strategies that include dosimetry and considerations of tumor burden. Such progress has generated pivotal studies that will establish the radiobiologic paradigms for successful radioimmunotherapy of solid tumors. This review will describe seminal studies that have paved the way to an understanding of radioimmunotherapy in solid tumors. Finally, the authors' views of the future of this promising cancer therapy will be presented.

Animals↗
PubMedDate not supplied

Effect of stent on radiation dosimetry in an in-stent restenosis model.

PURPOSE: Intravascular brachytherapy is the leading modality being evaluated for treatment of in-stent restenosis. Stent struts may have an effect on the dose distributions of various radiation sources. We evaluated dosimetry in a stented coronary artery model using a variety of beta and gamma sources and stent materials. METHODS: We determined the dose distributions with and without stent in the in-stent restenosis model. Three beta-particle emitting radionuclides, 90Y (2.3 MeV), 144Pr (3.0 MeV), and 106Rh (3.5 MeV), and two gamma-ray emitters, 192Ir (380 keV) and 125I (30 keV), were studied. Stent materials included stainless steel, nitinol, and tantalum. Monte Carlo dose calculations were performed in a stent model of multiple stent struts placed at 1.5 mm from the source. Isodose curves were generated and the ratios of dose rates with and without stent, the stent factors, were evaluated. A stent factor of greater or less than unity represents dose enhancement or reduction in the presence of a stent. RESULTS: For the three beta radionuclides, dose reduction was found on the adventitial side of the stent strut and dose enhancement was noted on the luminal side. On the luminal side, the maximum dose enhancement ranges from 7% to 29%, and the dose reduction on the adventitial side ranges from 13% to 43%. Both the reduction and enhancement effects were most pronounced for the high atomic number material, tantalum. For a given stent material, the dose reduction and enhancement are similar for the three beta radionuclides. For the gamma sources, the stent had no effect for the high-energy 192Ir, but for the low-energy 125I, drastic dose reduction on the adventitial side was observed (up to 86% for tantalum stent), and about 10% dose enhancement on the luminal side was also noted. The dose reduction with 125I was more pronounced than that seen with the beta sources. CONCLUSIONS: The presence of stent struts significantly affects dose distributions of 90Y, 106Rh, 144Pr, and 125I. The maximum dose reduction can be as much as 86%. 192Ir was unaffected. These factors need to be considered in choosing radionuclides and dose prescriptions in treating in-stent restenosis.

Brachytherapy↗
PubMed1976

Angiocardiography with iridium-191m: an ultrashort-lived radionuclide (T1/2 4.9 sec).

Iridium-191m is a potential tracer for angiocardiography and may be of particular value in the evaluation of heart disease in children. It possesses a short half-life (4.9 sec), suitable photon energy (129 keV) and may be obtained as a generator product by decay of its long lived (15.3 day) parent 191 Os. An 191Os leads to 191mIr generator capable of providing 15 mCi of 191mIr in 1.5 ml of eluant is described. The separation of 191mIr from 191Os is achieved by absorbing 191OsC16-2 on an anion exchange resin. The generator employs an additional resin column which is replaced to prevent 191Os breakthrough to become excessive. By this procedure, the breakthrough may be kept below 0.001% over a period of at least one month and after multiple elutions.

Angiocardiography↗
PubMed2006

Comparison of SPECT aerosol deposition data with twenty-four-hour clearance measurements.

Three-dimensional (3D) radionuclide imaging provides detailed information on the distribution of inhaled aerosol material within the body. Analysis of the data can provide estimates of the deposition per airway generation. Information on regional distribution of deposited aerosol can also be obtained from 24-hour clearance measurements. In this study, a nebulizer was used to deliver a radiolabeled aerosol to nine human subjects. Single photon emission computed tomography (SPECT) has been used to assess the distribution of aerosol deposition per airway generation. The deposition pattern was also estimated using measurements of the aerosol remaining in the lung 24 h after inhalation. The error in the SPECT value was assessed by simulation and that in the 24-h clearance value by repeat analysis. The mean fraction of lung deposition in the conducting airway (CADF) from SPECT was 0.21. The corresponding 24-h clearance value was 0.23. These values were not significantly different. There was a weak but non-significant correlation between the SPECT and 24-h measurements (r = 0.49). The standard error of the difference was 0.11. The corresponding errors on the SPECT and 24-h clearance measurements were 0.04 and 0.05, respectively. There was no systematic difference between the values of conducting airways deposition obtained from 24-h measurements and SPECT. However, there were random differences on individual subjects, which were larger than the estimated measurement errors.

Administration, Inhalation↗
PubMed2006

Analysis of novel soluble chromate and uranyl reductases and generation of an improved enzyme by directed evolution.

Most polluted sites contain mixed waste. This is especially true of the U.S. Department of Energy (DOE) waste sites which hold a complex mixture of heavy metals, radionuclides, and organic solvents. In such environments enzymes that can remediate multiple pollutants are advantageous. We report here evolution of an enzyme, ChrR6 (formerly referred to as Y6), which shows a markedly enhanced capacity for remediating two of the most serious and prevalent DOE contaminants, chromate and uranyl. ChrR6 is a soluble enzyme and reduces chromate and uranyl intracellularly. Thus, the reduced product is at least partially sequestered and nucleated, minimizing the chances of reoxidation. Only one amino acid change, (Tyr)128(Asn), was responsible for the observed improvement. We show here that ChrR6 makes Pseudomonas putida and Escherichia coli more efficient agents for bioremediation if the cellular permeability barrier to the metals is decreased.

Directed Molecular Evolution↗
PubMedDate not supplied

[Genetic disorders in the pollen cells of waxy barley in radioactive contamination after the Chernobyl accident].

Genotoxic effects during microsporogenesis and gametogenesis were studied in barley of the waxy strain grown on 3 experimental plots situated in the region of the Chernobyl disaster (plot 1 in the town of Chernobyl, plots 2 and 3 in the town of Yanov, 3 km away from the damaged power plant). It was determined that an increased level of radionuclide pollution and chronic irradiation during ontogenesis results in higher incidence of meiotic disturbances and abnormalities during formation of the male gametophyte. Incidence of waxy reversions in pollen grains depends on the activity of radionuclide pollutants as well. We suggest that selection affecting both diplont and haplont forms will provide for the absence of significant aberrations in subsequent plant generations.

Accidents↗
PubMed1987

[Pharmacokinetics of 99m Tc-technephyte in radionuclide studies of the liver and spleen].

The authors present the results of an experimental study of pharmacokinetics of a new Soviet drug 99 mTc-technephyte for scintigraphy of the liver and spleen. The results of biological distribution of the agent in rat, scintigrams of the liver and spleen in rabbits and dogs have shown a high accumulation of 99 mTc-technephyte in the liver (up to 90%). The agent is prepared within one stage from a kit of reagents and 99m-sodium pertechnetate obtained using a generator.

Animals↗
PubMedDate not supplied

[The dynamics of the allele variants of biochemical markers in generations of cattle in the exclusion zone of the Chernobyl Atomic Electric Power Station].

Analysis of the heritability of allelic variants of polymorphous genetic-biochemical systems in the cattle groups, reproduced in conditions of increased radionuclide pollution in exclusion zone of the Chernobyl AES was carried out. The disturbances of equal probability of the heritability for different allelic variants in some cattle group were revealed. It was supposed, that the appearance of the disturbances may take part in changeabilities of different gene pools under the conditions of ecological stresses. Possible mechanisms of this phenomenon were discussed.

Alleles↗
PubMed2000

Minimization and management of wastes from biomedical research.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue.

Biomedical Technology↗