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PubMed1975

Generator-produced 99m TcO4-: carrier free.

A solution of 99m-TCO4-minus, as eluted from a 99Mo-99mTc radionuclide generator contains a greater chemical quantity of technetium than that attributable to the metastable isomer alone. The isomeric transition of the radionuclide of interest, 99mTc, gives rise to a determinable and chemically significant quantity of technetium carrier, 99Tc. A method is presented for calculating the total chemical quantity of technetium in a generator eluate.

Molybdenum↗
PubMed2005

Production of actinium-225 for alpha particle mediated radioimmunotherapy.

The initial clinical trials for treatment of acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter (213)Bi in killing cancer cells. Bismuth-213 is obtained from a radionuclide generator system from decay of 10-days (225)Ac parent. Recent pre-clinical studies have also shown the potential application of both (213)Bi, and the (225)Ac parent radionuclide in a variety of cancer systems and targeted radiotherapy. This paper describes our five years of experience in production of (225)Ac in partial support of the on-going clinical trials. A four-step chemical process, consisting of both anion and cation exchange chromatography, is utilized for routine separation of carrier-free (225)Ac from a mixture of (228)Th, (229)Th and (232)Th. The separation of Ra and Ac from Th is achieved using the marcoporous anion exchange resin MP1 in 8M HNO(3) media. Two sequential MP1/NO(3) columns provide a separation factor of approximately 10(6) for Ra and Ac from Th. The separation of Ac from Ra is accomplished on a low cross-linking cation exchange resin AG50-X4 using 1.2M HNO(3) as eluant. Two sequential AG50/NO(3) columns provide a separation factor of approximately 10(2) for Ac from Ra. A 60-day processing schedule has been adopted in order to reduce the processing cost and to provide the highest levels of (225)Ac possible. Over an 8-week campaign, a total of approximately 100 mCi of (225)Ac (approximately 80% of the theoretical yield) is shipped in 5-6 batches, with the first batch typically consisting of approximately 50 mCi. After the initial separation and purification of Ac, the Ra pool is re-processed on a bi-weekly schedule or as needed to provide smaller batches of (225)Ac. The averaged radioisotopic purity of the (225)Ac was 99.6 +/- 0.7% with a (225)Ra content of < or =0.6%, and an average (229)Th content of (4(-4)(+5)) x 10(-5)%.

Actinium↗
PubMed2004

Engineered liposomes for potential alpha-particle therapy of metastatic cancer.

UNLABELLED: Disseminated, metastatic cancer is frequently incurable. Targeted alpha-particle emitters hold great promise as therapeutic agents for disseminated disease. (225)Ac is a radionuclide generator that has a 10-d half-life and results in alpha-emitting daughter elements ((221)Fr, (217)At, (213)Bi) that lead to the emission of a total of 4 alpha-particles. The aim of this study was to develop approaches for stable and controlled targeting of (225)Ac to sites of disseminated tumor metastases. Liposomes with encapsulated (225)Ac were developed to retain the potentially toxic daughters at the tumor site. METHODS: (225)Ac was passively entrapped in liposomes. To experimentally test the retention of actinium and its daughters by the liposomes, the gamma-emissions of (213)Bi were measured in liposome fractions, which were separated from the parent liposome population and the free radionuclides, at different times. Under equilibrium conditions the decay rate of (213)Bi was used to determine the concentration of (225)Ac. Measurements of the kinetics of (213)Bi activity were performed to estimate the entrapment of (213)Bi, the last alpha-emitting daughter in the decay chain. RESULTS: Stable pegylated phosphatidylcholine-cholesterol liposomes of different sizes and charge were prepared. Multiple (more than 2) (225)Ac atoms were successfully entrapped per liposome. (225)Ac retention by zwitterionic liposomes was more than 88% over 30 d. Retention by cationic liposomes was lower. A theoretical calculation showed that for satisfactory (213)Bi retention (>50%), liposomes of relatively large sizes (>650 nm in diameter) are required. (213)Bi retention was experimentally verified to be liposome-size dependent. For large liposomes, the measured (213)Bi retention was lower than theoretically predicted (less than 10%). CONCLUSION: This work supports the hypothesis that it may be possible to develop (225)Ac-based therapies by delivering multiple (225)Ac atoms in liposomes. Improvements in the retention of (225)Ac daughters will likely be necessary to fulfill this potential. Because of the size of the liposomal structures required to contain the daughters, the approach is ideally suited for locoregional therapy (e.g., intraperitoneal, intrahepatic artery, or intrathecal).

Actinium↗
PubMed1982

Performance of a fully automated program for measurement of left ventricular ejection fraction.

A fully automated program developed by us for measurement of left ventricular ejection fraction from equilibrium gated blood pool studies was evaluated in 130 additional patients. Both 6-min (130 studies) and 2-min (142 studies in 31 patients) gated blood pool studies were acquired and processed. The program successfully generated ejection fractions in 86% of the studies. These automatically generated ejection fractions were compared with ejection fractions derived from manually drawn regions of interest. When studies were acquired for 6-min with the patient at rest, the correlation between automated and manual ejection fractions was 0.92. When studies were acquired for 2-min, both at rest and during bicycle exercise, the correlation was 0.81. In 25 studies from patients who also underwent contrast ventriculography, the program successfully generated regions of interest in 22 (88%). The correlation between the ejection fraction determined by contrast ventriculography and the automatically generated radionuclide ejection fraction was 0.79.

Cardiac Output↗
PubMed1993

Intracoronary air-filled albumin microspheres for myocardial blood flow measurement.

OBJECTIVES: The aim of this study was to explore the possibility of quantifying coronary blood flow by myocardial contrast echocardiography with air-filled serum albumin microspheres (Albunex). BACKGROUND: Air-filled albumin microspheres have been proposed as an intravascular tracer for the study of myocardial perfusion by contrast echocardiography. METHODS: In six anesthetized open chest dogs, the left circumflex coronary artery was cannulated and perfused by a roller pump with blood from the femoral artery. Both air-filled albumin microspheres (0.4 ml, 2 x 10(8) spheres/ml) and technetium-99m-labeled albumin were injected as a bolus into the coronary cannula at baseline and after treatment with dipyridamole (0.56 mg/kg body weight intravenously for 4 min). Two-dimensional echographic images of the left ventricular short axis were digitized to generate myocardial time-intensity curves; myocardial radioactivity was measured by an external detector to generate radionuclide time-activity curves. RESULTS: After dipyridamole, left circumflex coronary artery blood flow (as measured by both the pump and an electromagnetic flow meter) significantly increased (from 1.06 +/- 0.28 to 3.61 +/- 1.43 ml/min per g of myocardium). Peak intensity and rise time of contrast echo curves were able to differentiate baseline myocardial perfusion from coronary hyperemia but did not show any significant correlation with coronary blood flow. A weak inverse correlation with coronary blood flow was provided by myocardial mean transit time of air-filled albumin microspheres (r = 0.33). Conversely, a close inverse correlation with coronary blood flow was obtained by myocardial mean transit time of technetium-99m-labeled albumin (r = 0.95). Myocardial transit time of air-filled albumin microspheres (1.95 +/- 0.60 s) was also markedly shorter than that of labeled albumin (5.35 +/- 3.43 s, p < 0.001) and the measurements were less reproducible. CONCLUSIONS: In this experimental study, coronary blood flow was not adequately quantified by myocardial contrast echocardiography with intracoronary injection of air-filled albumin microspheres.

Albumins↗
PubMed2005

(83m)Kr radioactive source based on (83)Rb trapped in cation-exchange paper or in zeolite.

The mono-energetic conversion electrons from the decay of (83m)Kr represent a unique tool for energy calibration and systematic studies of the tritium beta spectrum measured in neutrino mass determination experiments. For this reason, the corresponding parent isotope was produced in reactions (nat)Kr(p,xn)(83)Rb. The behaviour of (83)Rb (T(1/2)=86.2d) and its daughter product (83m)Kr (T(1/2)=1.83h) was examined, when the (83)Rb was trapped in a cation-exchanger chromatographic paper or in zeolite. Using gamma spectroscopy measurements, recommendations for the production of a (83)Rb/(83m)Kr radionuclide generator based on these cation-exchangers and suitable for the neutrino mass determination experiment KATRIN were deduced.

Journal Article↗
PubMedDate not supplied

Monte Carlo analysis of multi-layer targets for production of 15O.

A Monte Carlo simulation code was written to analyze multi-layer targets for production of 15O. The code models beam-particle transport through the target and production and transport of generated radionuclides; it can be used to assess the effects on radionuclide production of several beam and target design variables. A pathlength correction feature is included that relaxes restrictions inherent in previous ion transport codes and a variance reduction procedure is implemented that significantly improves code efficiency.

Monte Carlo Method↗
PubMed2005

Production of Ac-225 from Th-229 for targeted alpha therapy.

This work describes a method for the separation and purification of Ac-225 from a Th-229 source. The procedure is based on the combination of ion exchange and extraction chromatographic methods in nitric acid media and allows the preparation of carrier-free, clinical grade Ac-225 with an overall yield exceeding 95%. Quality control of the product is performed using radiometric (alpha, gamma spectrometry) and mass spectrometric methods. The Ac-225 product can be loaded on a radionuclide generator for the preparation of Bi-213 for preclinical and clinical studies of targeted alpha therapy of cancer and infectious diseases.

Actinium↗
PubMed2006

Future direction of renal positron emission tomography.

Positron emission tomography (PET) is perfectly suited for quantitative imaging of the kidneys, and the recent improvements in detector technology, computer hardware, and image processing software add to its appeal. Multiple positron emitting radioisotopes can be used for renal imaging. Some, including carbon-11, nitrogen-13, and oxygen-15, can be used at institutions with an on-site cyclotron. Other radioisotopes that may be even more useful in a clinical setting are those that either can be obtained from radionuclide generators (rubidium-82, copper-62) or have a sufficiently long half-life for transportation (fluorine-18). The clinical use of functional renal PET studies (blood flow, glomerular filtration rate) has been slow, in part because of the success of concurrent technologies, including single-photon emission computed tomography (SPECT) and planar gamma camera imaging. Renal blood flow studies can be performed with O-15-labeled water, N-13-labeled ammonia, rubidium-82, and copper-labeled PTSM. With these tracers, renal blood flow can be quantified using a modified microsphere kinetic model. Glomerular filtration can be imaged and quantified with gallium-68 EDTA or cobalt-55 EDTA. Measurements of renal blood flow with PET have potential applications in renovascular disease, in transplant rejection or acute tubular necrosis, in drug-induced nephropathies, ureteral obstruction, before and after revascularization, and before and after the placement of ureteral stents. The most important clinical application for imaging glomerular function with PET would be renovascular hypertension. Molecular imaging of the kidneys with PET is rather limited. At present, research is focused on the investigation of metabolism (acetate), membrane transporters (organic cation and anion transporters, pepT1 and pepT2, GLUT, SGLT), enzymes (ACE), and receptors (AT1R). Because many nephrological and urological disorders are initiated at the molecular and organelle levels and may remain localized at their origin for an extended period of time, new disease-specific molecular probes for PET studies of the kidneys need to be developed. Future applications of molecular renal imaging are likely to involve studies of tissue hypoxia and apoptosis in renovascular renal disease, renal cancer, and obstructive nephropathy, monitoring the molecular signatures of atherosclerotic plaques, measuring endothelial dysfunction and response to balloon revascularization and restenosis, molecular assessment of the nephrotoxic effects of cyclosporine, anticancer drugs, and radiation therapy. New radioligands will enhance the staging and follow-up of renal and prostate cancer. Methods will be developed for investigation of the kinetics of drug-delivery systems and delivery and deposition of prodrugs, reporter gene technology, delivery of gene therapy (nuclear and mitochondrial), assessment of the delivery of cellular, viral, and nonviral vectors (liposomes, polycations, fusion proteins, electroporation, hematopoietic stems cells). Of particular importance will be investigations of stem cell kinetics, including local presence, bloodborne migration, activation, seeding, and its role in renal remodeling (psychological, pathological, and therapy induced). Methods also could be established for investigating the role of receptors and oncoproteins in cellular proliferation, apoptosis, tubular atrophy, and interstitial fibrosis; monitoring ras gene targeting in kidney diseases, assessing cell therapy devices (bioartificial filters, renal tubule assist devices, and bioarticial kidneys), and targeting of signal transduction moleculas with growth factors and cytokines. These potential new approaches are, at best, in an experimental stage, and more research will be needed for their implementation.

Forecasting↗
PubMed2003

Age-specific uncertainty of the 131I ingestion dose conversion factor.

The production of weapons-grade nuclear materials and their by-products has resulted in a number of releases from United States Department of Energy facilities. 131I, a fission by-product, is one of the most common radionuclides generated and released to the environment. It is known that there are differences in various physiological parameters over all age groups when considering biokinetic modeling of iodine. The establishment of age-specific dose conversion factor uncertainty is necessary for accurate internal dose assessment. The 131I dose conversion factor determined herein is log-normally distributed with varying age-specific distribution characteristics. The two most important parameters for determination of the dose conversion factor, in all age groups, are thyroid mass and iodine uptake fraction. These parameters are assumed to be highly correlated with a relationship that is quite important to dose conversion factor uncertainty. Dose estimates to individuals exposed to radioiodine can be determined more accurately with an increased understanding of the correlation between thyroid mass and uptake fraction. Improved dose estimates following oral intakes of 131I can be made from the consideration of age-specific dose conversion factors and their input parameters.

Administration, Oral↗
PubMed1981

The accuracy of 99Molybdenum assays in 99mTechnetium solutions.

A study was performed to determine the accuracy of 99Mo measurements using three commercial dose calibrators with their 99Mo assay shields. One 99Mo assay shield allowed excessive penetration by the lower energy 99mtc photons, resulting in the calibrator's falsely high interpretation of the activity of 99Mo present in the high-activity 99mTc eluates. All three calibrators performed adequately with a National Bureau of Standards 99Mo standard in equilibrum with 99mTc. By using low-activity aliquots of 99Mo and 99mTc, a low-level linearity test was performed. Two of the calibrators were found to have a threshold of approximately 10 microCi (370 kBq) for a nonzero 99Mo response, although one of these occasionally produced variable nonzero responses below its threshold. Only one of the calibrators was found to reflect accurately the activity of 99Mo present under all conditions tested.

Calibration↗
PubMed1991

National emission standards for hazardous air pollutants--EPA. Final rule.

Today EPA is staying the effectiveness of subpart I of 40 CFR part 61, the National Emission Standards for Hazardous Air Pollutants for Radionuclide Emissions (54 FR 51654, December 15, 1989) as applied to facilities licensed by the Nuclear Regulatory Commission or an Agreement State ("NRC-licensed facilities"), other than nuclear power reactors, until November 15, 1992. The purpose or this rule is to afford EPA the time required to make an initial determination pursuant to section 112(d)(9) of the 1990 Clean Air Amendments before subpart I becomes effective for such facilities. EPA intends to propose a rule pursuant to section 112(d)(9) to rescind subpart I for nuclear power reactors, and to take final action no later than June 30, 1991, concerning a separate proposal to stay the effectiveness of subpart I for nuclear power reactors during the pendency of the rulemaking on recission. This rule staying subpart I for NRC-licensed facilities other than nuclear power reactors, and the Agency's final action on its proposal to stay subpart I for nuclear power reactors, will completely supplant all stays previously entered for such facilities during the Agency's reconsideration of subpart I under Clean Air Act section 307(d)(7)(B).

Air Pollutants↗
PubMed1985

DTPA-coupled antibodies labeled with yttrium-90.

Yttrium-90 has been described as one of the best radionuclides for tumor therapy when chelated to tumor-associated antibodies. This evaluation is based on the superior properties of this radionuclide (suitable half-life, pure beta-ray emitter of intermediate energy, stable daughter, and suitable chemical properties) and because it is available as a radionuclide generator product by decay of its 28-yr parent 90Sr. We have determined that 90Y obtained from one such generator is suitable for labeling antibodies coupled with DTPA. Furthermore, we have shown that the dissociation rate of [90Y]DTPA-IgG in serum at 37 degrees C is similar to that of [111In]DTPA-IgG at about 8-9%/day. Biodistribution studies of 111In- and 90Y-labeled to DTPA-coupled IgG show that the labels distribute nearly identically at 1 hr postadministration, although differences in distribution are apparent at 24 hr. It is possible that these differences reflect the redistribution of the labels following catabolism at the site of localization.

Animals↗