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At least 433 records · Page 24Linked to original sources
PubMed1997

Comparison of the biodistribution and the efficacy of monoclonal antibody 323/A3 labeled with either 131I or 186Re in human ovarian cancer xenografts.

PURPOSE: The radionuclide 186Re has favorable physical characteristics for use in radioimmunotherapy, including the emission of beta-particles of a high-energy and a low-abundance of gamma-emission. The gamma-emission, in particular, is ideal for tumor imaging and poses less hazards to the patient and the medical personnel when compared with the gamma-emission of the widely used radionuclide 131I. In the present study, we determined whether 186Re-labeled monoclonal antibody 323/A3 may be better suited for the treatment of ovarian cancer than 131I-323/A3. METHODS AND MATERIALS: We compared the biodistribution and the efficacy of 186Re- and 131I-labeled 323/A3 in nude mice bearing s.c. the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. 186Re was conjugated to 323/A3 with the use of the S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) chelate. RESULTS: A molar ratio of Re-MAG3:323/A3 of 3:1 did not affect the integrity and the pharmacokinetic behaviour of the MAb. The tumor uptake and the retention of 186Re- and 131I-labeled 323/A3 were comparable, but the cumulative absorbed radiation dose in the tumor delivered by 186Re-323/A3 was 1.3-fold higher than that of 131I-323/A3. When mice were treated with equivalent radionuclide doses, the tumor growth inhibition induced by 186Re-323/A3 was similar or slightly better when compared with the efficacy of 131I-323/A3. When mice were treated with radionuclide doses that were adjusted to obtain equal cumulative absorbed radiation doses in the tumor for both conjugates, 131I-323/A3 was slightly more effective in the inhibition of the growth of FMa and OVCAR-3 xenografts. CONCLUSIONS: The favorable physical characteristics of 186Re as well as its efficacy when conjugated to a MAb indicate 186Re as an attractive radionuclide in radioimmunotherapy of ovarian cancer patients.

Animals↗
PubMed1998

Current status of radioactive stents for the prevention of in-stent restenosis.

PURPOSE: The objective of this paper was to provide an update on the clinical and experimental evaluation of radioactive stents for the prevention of restenosis. MATERIALS AND METHODS: Direct ion implantation of 32P onto the surface of a 15-mm length balloon expandable stainless-steel Palmaz-Schatz stent was employed to render this commercially available vascular stent radioactive. 32Phosphorous, a pure beta-particle-emitting radioisotope, was selected because of its short half-life (14.3 days) and limited range of tissue penetration (3-4 mm). The vascular response to radioactive 7-mm length Palmaz-Schatz stents with activities 0.14 to 23 microCi of 32P were evaluated in animal models of arterial injury and restenosis. The Phase-1 isostent for restenosis intervention study (IRIS trial) was a nonrandomized safety trial designed to evaluate the use of a low activity 32P (0.5 to 1.5 microCi) 15-mm length Palmaz-Schatz stent for the treatment of de novo or restenosis native coronary arterial lesions. RESULTS: In the porcine coronary restenosis model, at < or =0.5 microCi and > or =3.0 microCi stent activities, there was a 30% reduction in the neointimal and percent area stenosis as compared to nonradioactive stents. The 1.0 microCi stents, however, had nearly 2-fold greater neointimal formation and more luminal narrowing than the control stents. In the Phase 1 IRIS trial, 57 patients with symptomatic de novo or restenosis native coronary lesions have been treated with low activity (0.5 to 1.5 microCi) 32P Palmaz-Schatz coronary stents. Fifty-seven stents were successfully implanted without a major procedural complication (death, urgent coronary bypass, Q-wave myocardial infarction). There were no cases of stent thrombosis, target vessel revascularization, or other adverse events in the first 30 days after implant. CONCLUSION: The early clinical results with a low-activity 32P Palmaz-Schatz radioactive stent demonstrate sufficient procedural and 30-day event-free survival to warrant consideration of additional clinical studies to determine the safety and efficacy of this therapy for the prevention of restenosis. Future studies will focus on optimal stent design for delivery of radiation, and will further evaluate safe and effective dosing strategies.

Animals↗
PubMed2003

Characterization of solidified reverse micellar solutions (SRMS) and production development of SRMS-based nanosuspensions.

Solidified reverse micellar solutions (SRMS), i.e. binary mixtures of 30-60% (w/w) lecithin and two different hard fats, were investigated regarding their physicochemical properties and the influence of lecithin on solid lipids. For this purpose, the systems were characterized with X-ray and thermal analysis, transmission electron microscopy (TEM) and photon correlation spectroscopy. The melting point (m.p.) of the solid lipids, which is a crucial parameter of the solid state, was not altered up to a lecithin concentration of 50% whereas reverse micelles were likely to be frozen still in the solid state. In addition, solubilities of 17beta-oestradiol-hemihydrate, pilocarpine base and hydrochloride in the SRMS melt were studied for evaluation of the drug carrier potency. Drug solubilization in the SRMS melt increased linearly with rising amount of lecithin. SRMS-based nanosuspensions were developed with a given lecithin/hard fat ratio of 1:1 (w/w). High-pressure homogenization was applied on cold to avoid lecithin loss. Optimization of the systems in terms of a variation of the homogenizing parameters such as pressure, number of cycles and temperature resulted in nanoparticulate systems with a polysorbate 80/SRMS ratio of 1:5 (w/w), and a total amount of 5 and 15% (w/w) SRMS, respectively. Production temperatures near the lipid m.p. proved best to be maintained by varying the pressure, yielding small nanoparticles with a narrow particle size distribution. The solid lipid nanoparticles were characterized with X-ray and thermal analysis as well as TEM. The crystalline particles (beta modification) are of anisometrical shape and have transition temperatures far below the bulk m.p. due to the colloidal character of the systems.

Calorimetry, Differential Scanning↗
PubMed2000

Application of a low-background gamma-ray spectrometer to the determination of 90Sr

A method for quantitative determination of 90Sr with a germanium gamma-ray spectrometer is presented. The bremsstrahlung energy spectrum produced by high-energy beta particles from the 90Sr source encapsulated in a given absorbing material is measured. The idea was tested on various types of low-background germanium gamma-ray spectrometers. The optimisation of absorber thickness for aluminium, iron, copper, cadmium, tantalum and lead is presented. The lowest achieved detection limit for a 10% efficiency HPGe detector was 0.38 Bq/sample which allows this method to be applied to some environmental studies.

Journal Article↗
PubMed2000

Accelerator mass spectrometry analyses of environmental radionuclides: sensitivity, precision and standardisation

Accelerator Mass Spectrometry (AMS) is the analytical technique of choice for the detection of long-lived radionuclides which cannot be practically analysed with decay counting or conventional mass spectrometry. AMS allows an isotopic sensitivity as low as one part in 10(15) for 14C (5.73 ka), 10Be (1.6 Ma), 26Al (720 ka), 36Cl (301 ka), 41Ca (104 ka), 129I (16 Ma) and other long-lived radionuclides occurring in nature at ultra-trace levels. These radionuclides can be used as tracers and chronometers in many disciplines: geology, archaeology, astrophysics, biomedicine and materials science. Low-level decay counting techniques have been developed in the last 40-50 years to detect the concentration of cosmogenic, radiogenic and anthropogenic radionuclides in a variety of specimens. Radioactivity measurements for long-lived radionuclides are made difficult by low counting rates and in some cases the need for complicated radiochemistry procedures and efficient detectors of soft beta-particles and low energy x-rays. The sensitivity of AMS is unaffected by the half-life of the isotope being measured, since the atoms not the radiations that result from their decay, are counted directly. Hence, the efficiency of AMS in the detection of long-lived radionuclides is 10(6)-10(9) times higher than decay counting and the size of the sample required for analysis is reduced accordingly. For example, 14C is being analysed in samples containing as little as 20 microg carbon. There is also a world-wide effort to use AMS for the analysis of rare nuclides of heavy mass, such as actinides, with important applications in safeguards and nuclear waste disposal. Finally, AMS microprobes are being developed for the in-situ analysis of stable isotopes in geological samples, semiconductors and other materials. Unfortunately, the use of AMS is limited by the expensive accelerator technology required, but there are several attempts to develop compact AMS spectrometers at low (< or = 0.5 MV) terminal voltages. Recent advances in AMS will be reviewed with highlights from the scientific programs at Lucas Heights and other AMS centres.

Journal Article↗
PubMed2000

NaI detector neutron activation spectra for PGNAA applications

When NaI detectors are used in prompt gamma-ray neutron activation analysis devices, they are activated by neutrons that penetrate the detector. While thermal neutron filters like boron or lithium can be used to reduce this activation, it can never be completely eliminated by this approach since high energy neutrons can penetrate the detector and thermalize inside it. This activation results in the emission of prompt gamma rays from both the I and Na and the production of the radioisotopes 128I and 24Na that subsequently decay and emit their characteristic beta particles and gamma rays. The resulting three spectra represent a background for this measurement. An experimental method for obtaining these three spectra is described and results are reported for 2" x 2", 5" x 5", 6" x 6", and 1" x 6" NaI detectors using the thermal neutron beam of the NCSU PULSTAR nuclear reactor. In addition, Monte Carlo simulation programs have been developed and used for simulating these spectra. Good results have been obtained by the Monte Carlo method for the two radioisotope spectra, and it is anticipated that good results will also be obtained for the prompt gamma-ray spectrum when the I and Na coincidence schemes are known.

Journal Article↗
PubMedDate not supplied

Analytical calculations of counting losses in internal gas proportional counting.

In internal gas proportional counting, the evaluation of counting losses is important in order to obtain high accuracy measurement results. In this paper, counting losses due to the wall effect and not counted beta particles with very low energy are evaluated by analytical calculations. The calculated and experimental results are compared and a very good agreement is found.

Journal Article↗
PubMedDate not supplied

The absolute counting of 166mHo, 58Co and 88Y.

In this study, absolute 4pi beta-gamma-coincidence counting was used to measure the mass activity of 166mHo, 58Co and 88Y. For 166mHo and 88Y, three gamma windows were set to study the systematic error caused by the different gamma window settings. To eliminate the effect arising from the large difference in counting efficiency of the 4pi beta counter between electron capture events and beta+ particles, the two-dimensional extrapolation method was used to measure 58Co. The measurement results for the three nuclides were linked with the BIPM SIR through two APMP regional comparisons, APMP.RI(II)-K2, Ho-166m and APMP.RI(II)K2.Co-58, Y-88. Results are presented.

Journal Article↗
PubMed2000

Importance of covariances for uncertainty estimates in measurement of radionuclide mixtures by multichannel counting.

Multichannel counting is often used when samples containing a mixture of known radionuclides are measured. Solutions to this method have been presented but to our knowledge, none of them took into account the covariances for evaluating the uncertainty of measurement. This paper presents new solutions for estimating uncertainties in measurement of radionuclide mixtures by multichannel counting and shows that covariances may contribute significantly to uncertainty of measurement so that they must be evaluated.

Alpha Particles↗
PubMed2000

Systemic radiation therapy with unsealed radionuclides.

Systemic unsealed radiation therapy is achieved when a radioactive substance is administered orally or parenterally and that material is concentrated in an organ or site for sufficient time to deliver a therapeutic dose of radiation. The radioactive material usually emits beta particles. In general, there is intense local radiation of the abnormal tissues, and normal organs, which do not trap the radioactive material, are exposed to a small radiation dose. The most frequent treatments involve radioiodine (131)I for hyperthyroidism and differentiated thyroid cancer. Other applications include treatment of painful skeletal metastases, polycythemia vera, malignant cysts, and neuroendocrine tumors. The treatments are usually well tolerated and not associated with long-term effects, such as cancer or infertility.

Arthritis↗
PubMedDate not supplied

Dosimetry for an Sr90/Y90 source train used for intravascular radiation of a hemodialysis graft.

OBJECTIVE: Vascular access for hemodialysis is often achieved with an arterial-venous graft (AVG). Brachytherapy is being explored for prevention of stenosis within these grafts. The objective was to develop treatment planning (TP) capability for dialysis implants. MATERIALS AND METHODS: Fluoroscopic images are used to identify position of sources and irradiated vessel. An Sr(90)/Y(90) beta source, jacketed in a CO(2)-filled balloon, is used to irradiate the AVG. A single-seed Sr(90) dose kernel was generated using Monte Carlo. The single-seed dose kernel was employed to calculate the dose surrounding the implant accounting for the path length of the beta particles through the gas-filled balloon. RESULTS: Dose distributions are displayed superimposed on the fluoroscopic image of the AVG. Dose-area histograms were also generated. CONCLUSION: TP for dialysis implants can be performed using radiographic localization of the graft. The TP tools could be used to correlate clinical outcome with dose delivery.

Algorithms↗
PubMed2005

Radioluminescent light source for the development of optical sensor arrays.

A radioluminescent (RL) light source is evaluated for the development of photonically based chemical-responsive sensor arrays (CRSAs). The RL light source is comprised of a strontium-90 (90Sr) radionuclide and a plastic scintillator. The beta particles emitted from the 90Sr generate blue light (lambda(max) = 435 nm) from the plastic scintillator, and the blue light excites the analyte-responsive luminophores within the CRSA. To assess the RL light source utility, we have determined the analytical figures of merit from two tris(4,7'-diphenyl-1,10'-phenathroline)ruthenium(II)-doped xerogel-based sensor platforms: (i) a planar 5 x 5 multielement array and (ii) a discrete sensor element formed on the proximal face of poly(styrene) pillars that have a frustrated cone (frustum) geometry. We compare the performance from each platform when it is excited by a He-Cd laser (442 nm), a blue light-emitting diode (460-470 nm), and the RL light source. The RL light source yields results that are statistically equivalent to results from either electrically powered light source. The RL light source consumes no electrical power, is compact and simple, and has an extremely stable time-averaged signal. The primary trade-offs for these advantages are the RL light source's lower radiant power and the corresponding longer data acquisition times.

Journal Article↗
PubMed1998

Cerenkov radiation as a UV and visible light source for time-resolved fluorescence.

We demonstrate the first use of Cerenkov radiation for the measurement of fluorescence lifetimes. Relativistic beta particles from the nuclear decay of 90 Sr and 90Y generate a spectral continuum in a quartz waveguide. Light flashes of < 100-ps duration are delivered simultaneously to a sample cell and a reference photomultiplier. A simple, digitally based cross-correlation signal processor allows extraction of the sample fluorescence decay kinetics without distortions which can result from the random excitation pulse sequence. We characterize both the pulse duration and the pulse intensity of the light that is emitted from the waveguide. Although the excitation intensity is very weak, we demonstrate that accurate lifetime measurements are possible with only a few hundred seconds of integration time. Tests on a variety of compounds illustrate the utility of the light source throughout the UV and blue regions of the spectrum. We also discuss future design improvements and potential applications of this new approach to time-resolved fluorescence.

Fluorescence↗
PubMed2001

The effect of DFMO induced uptake of [3H] putrescine on human glioma cells.

Polyamine synthesis inhibitors, such as a-difluoromethylornithine (DFMO), inhibit tumor cell growth in vitro and in vivo. However, upon cessation of treatment, tumor growth resumes. We hypothesized that incorporation of radioactive polyamines might kill the growth-arrested cells. This hypothesis was previously tested in rat 9L brain tumor cells in which DFMO increased both the uptake and the retention of [3H] putrescine. In these rat cells, DFMO-induced retention of high-specific-activity [3H] putrescine for 20 days resulted in several logs killing. In the present studies all of the 5 different human glioma cell lines tested with DFMO treatment also showed enhanced uptake of exogenous [3H] putrescine, reduced cell counts and enhanced killing of colony forming cells (CSF). Extending the time of DFMO treatment of cells that had taken up high-specific-activity (80 Ci/mmol) [3H] putrescine further increased the killing. A 10-day extension resulted in a 10,000-fold reduction in cumulative cell growth. A 5-day extension resulted in a 2-3 log decrease in numbers of surviving CFC. These data further support the hypothesis and suggest that DFMO-induced cell cycle arrest enhances cellular retention of [3H] putrescine, increasing the effective internal radiation dose enough to cause proliferative death. In a clinical setting, the short (approximately 1 microm) path-length of the tritium beta particle should limit effects to the tumor cells and spare adjacent normal cells. These results support the concept that treatment with the combination of polyamine inhibitors and radioactive polyamines might be a useful adjunct to current therapies for glioblastoma multiforme.

Biological Transport↗
PubMed1983

Response of intestinal cells of differing topographical and hierarchical status to ten cytotoxic drugs and five sources of radiation.

The spacial distribution of cell death among the epithelial cells lining the adult mammalian small intestinal mucosa at various times after a range of doses of 10 different drugs as well as after internal or external irradiation (beta particles from tritium, gamma- and X-rays and neutrons) has been recorded. Cell death, expressed as pycnosis or apoptosis, has been recorded for each cell position up the side of the crypts of the small intestine. The results, in the form of distributions of dead cells at each cell position, show that each of the various cytotoxic agents tends to act preferentially over a characteristic small range of cell positions. Since cell position is likely to be related to hierarchical cell position within a family tree or cell lineage, each agent tends to act with greatest efficiency on cells at a particular position within the lineage. Adriamycin and the various forms of radiation tend to kill cells preferentially at cell position 4-5 i.e. on cells very early in the lineage, probably stem cells. Isopropyl-methane-sulphonate, nitrogen mustard and possibly Actinomycin-D act on cell position 6-7, while 5-fluorouracil, Myleran, cyclophosphamide, and cycloheximide tend to kill cells at cell position 7-9. Vincristine and hydroxyurea are the 2 agents that exhibit a specificity for cells highest up the crypt, i.e. latest in transit population of the cell lineage by acting on cell positions 10 or 11. The data also suggest that normal healthy cells continue to migrate up the crypt and onto the villus in spite of considerable cell death and reduced cell production.

Animals↗
PubMed1976

A simple method for the differential measurement of 125I and 3H by liquid-scintillatin spectrometry.

1. A method is described for the differential radioactivity counting of 125I and 3H in a liquid-scintillation spectrometer without a separate gamma counter. 2. The sample was contained in a polyethylene miniature vial placed centrally in a standard 20 ml glass scintillation vial containing a tin-loaded scintillant. 3. A direct measure of the 125I radioactivity at an efficiency of 30% was then obtained by radioactivity counting in the pre-set 3H window of a scintillation spectrometer. No counts for 3H radioactivity were registered at this stage because of the barrier to the passage of the low-energy beta-particles provided by the wall of the polyethylene vial. 4. After mixing the sample and scintillant both 125I and 3H were detected at efficiencies of 73% and 29% respectively. Subtraction of the 125I contribution from the combined radioactivity count rate then gave the net 3H count.

Humans↗
PubMed2003

The clinical importance of dosimetry in radioimmunotherapy with tositumomab and iodine I 131 tositumomab.

Radioimmunotherapy (RIT) is a promising emerging therapy for non-Hodgkin's lymphoma and may ultimately prove useful in the treatment of other tumors. The most extensively investigated RIT agent is tositumomab and iodine I 131 tositumomab (Bexxar; Corixa Corp, South San Francisco, CA, and GlaxoSmithKline, Philadelphia, PA) which has been administered to over 1,000 patients during the past 9 years. As with most drugs, there is considerable interpatient variability in the clearance rate (or total body residence time) of radioimmunoconjugates. The clearance rate of iodine I 131 tositumomab in clinical trials has varied by as much as five-fold. The advantage of RIT with iodine-131, which emits both gamma photons and beta particles, is that by scanning it allows for the determination of the patient-specific total body residence time by the administration of a trace-labeled dose of the radionuclide (ie, dosimetric dose). By administration of the dosimetric (trace-labeled) dose, and determination of the patient's residence time (a measure of how long the radionuclide is retained in the body), the therapeutic dose can be precisely adjusted to maximize the therapeutic effect and minimize toxicity. Tositumomab and iodine I 131 tositumomab is a specific therapeutic at two levels: first, it specifically targets the tumor, delivering a log or more radiation to tumor compared with the rest of the body; and second, the administered dose of radioactivity is patient-specific. The paradigm of a targeted drug with a patient-specific dose may become more routine as targeted therapies are further developed along with better assays to directly measure drug levels. For the present, whole-body dosimetry is routinely applied for RIT with tositumomab and iodine I 131 tositumomab and has proven to be a reliable method to determine the patient-specific maximally tolerated therapeutic radiation dose to maximize efficacy while minimizing organ and bone marrow toxicity.

Antibodies, Monoclonal↗