338 research outputs found
Ring laser angle encoder
Ring laser angle encoder with a scanning photometer autocollimator and an isolation axis, provides continuous digital readout. It measures the angular difference in inertial attitudes of target /any phenomena generating or reflecting a light beam/ two at a time relative to target one at a time
The Half-lives of La and La
The half-lives of La and La were determined via gamma
spectroscopy and high-precision ionization chamber measurements. The results
are 18.930(6) h for La and 4.59(4) h for La compared to the
previously compiled values of 19.5(2) h and 4.8(2) h, respectively. The new
results represent an improvement in the precision and accuracy of both values.
These lanthanum isotopes comprise a medically interesting system with positron
emitter La and Auger electron emitter La forming a matched pair
for internal diagnostics and therapeutics. The precise half-lives are necessary
for proper evaluation of their value in medicine and for a more representative
tabulation of nuclear data.Comment: 11 pages, 3 figure
An approach to description logic with support for propositional attitudes and belief fusion
The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-540-89765-1_8Revised Selected and Invited Papers of ISWC International Workshops, URSW 2005-2007.In the (Semantic) Web, the existence or producibility of certain, consensually agreed or authoritative knowledge cannot be assumed, and criteria to judge the trustability and reputation of knowledge sources may not be given. These issues give rise to formalizations of web information which factor in heterogeneous and possibly inconsistent assertions
and intentions, and make such heterogeneity explicit and manageable for reasoning mechanisms. Such approaches can provide valuable metaknowledge in contemporary application fields, like open or distributed ontologies, social software, ranking and recommender systems, and domains with a high amount of controversies, such as politics and culture. As an approach to this, we introduce a lean formalism for the Semantic
Web which allows for the explicit representation of controversial individual and group opinions and goals by means of so-called social contexts, and optionally for the probabilistic belief merging of uncertain or conflicting statements. Doing so, our approach generalizes concepts such as provenance annotation and voting in the context of ontologies and other kinds of Semantic Web knowledgeThis work was partially funded by the German National Research Foundation DFG (Br609/13-1, research project âOpen Ontologies and Open Knowledge Basesâ) and by the Spanish National Plan of R+D, project no. TSI2005-08225-C07-0
Production and isolation of 72As from proton irradiation of enriched 72GeO2 for the development of targeted PET/MRI agents
Introduction
Two current major research topics in nuclear medicine are in the development of long-lived positron-emitting nuclides for imaging tracers with long biological half-lives and in theranostics, imaging nuclides which have a chemically analogous therapy isotope. As shown in TABLE 1, the radioisotopes of arsenic (As) are well suited for both of these tasks with several imaging and therapy isotopes of a variety of biologically relevant half-lives accessible through the use of small medical cyclotrons. The five naturally abundant isotopes of germanium are both a boon and challenge for the medical nuclear chemist. They are beneficial in that they facilitate a wide array of producible radioarsenic isotopes. They are a challenge as monoisotopic radioarsenic production requires isotopically-enriched targets that are expensive and of limited availability. This makes it highly desirable that the germanium target material is reclaimed from arsenic isolation chemistry.
One major factor which has limited the development of radioarsenic has been difficulties in its incorporation into biologically relevant targeting vectors. Previous studies have labeled antibodies and polymers through covalent bonding of arsenite (As(III)) with the sulfydryl group1,2,3. Recent work in our group has shown the facile synthesis and utility of superparamagnetic iron oxide nanoparticle- (SPION-)bound radioarsenic as a dual modality positron emission tomography (PET)/magnetic resonance imaging (MRI) agent4.
Presently, we have built upon previous studies producing, isolating, and labeling untargeted SPION with radioarsenic4,5. We have incorp-rated the use of isotopically-enriched 72GeO2 for the production of radioisotopically pure 72As. The bulk of the 72GeO2 target material was re-claimed from the arsenic isolation chemical procedure for reuse in future irradiations. The 72As was used for ongoing development toward the synthesis of targeted, As-SPION-based, dual-modality PET/MRI agents.
Material and Methods
Targets of ~100 mg of isotopically-enriched 72GeO2 (96.6% 72Ge, 2.86% 73Ge, 0.35% 70Ge, 0.2% 74Ge, 0.01% 76Ge, Isoflex USA) were pressed into a niobium beam stop at 225 MPa, covered with a 25 ”m HAVAR containment foil, attached to a water-cooling target port, and irradiated with 3 ”A of 16.1 MeV protons for 2â3 hours using a GE PETtrace cyclotron. After irradiation, the target and beam stop were assembled into a PTFE dissolution apparatus, where the 72GeO2 target material was dissolved with the addition of 2 mL of 4 M NaOH and subsequent stirring. After dissolution was completed, the clear, colorless solution was transferred to a fritted glass column and the bulk 72GeO2 was reprecipitated by neutralizing the solution with the addition of 630 ”L [HCl]conc, filtered, and rinsed with 1 mL [HCl]conc. To the combined 72As-containing filtrates, 100 ”L 30% H2O2 was added to ensure that 72As was in the nonvolatile As(V) oxidation state. The ~3 mL solution was then evaporated at 115 ËC while the vessel was purged with argon, followed by a second addition of 100 ”L H2O2 after the volume was reduced to 1 mL. When the filtrate volume was ~0.3 mL, the vessel was removed from heat, allowed to cool with argon flow, and the arsenic reconstituted in 1 mL [HCl]conc and loaded onto a 1.5 mL bed volume Bio-Rad AG 1Ă8, 200â400 mesh anion exchange column preconditioned with 10 M HCl. The radioarsenic was eluted in 10 M HCl in the next ~10 mL, with 90% of the activity eluting in a 4 mL fraction. The column was then eluted with 5 mL 1 M HCl. The 72As-rich 10 M HCl fraction was reduced to As(III) with the addition of ~100 mg CuCl, and heating to 60 ËC for 1 hour. The resulting AsCl3 was then extracted twice into 4 mL cyclohexane, which were combined and back extracted into 500 ”L of water as As(OH)3.
This solution of 72As in H2O was then used directly to label SPION and for subsequent experiments conjugating 72As-SPION with TRC105, an angiogenesis-marking monoclonal antibody (MAb) targeting endoglin/CD105. Several methods were initially attempted involving directly conjugating the surface-modified SPION to the MAb through a polyethylene glycol (PEG) linker. More recent studies have investigated the radioarsenic labeling of SPION encapsulated in hollow mesoporous silica nanoparticles (SPION@HMSN) and its subsequent conjugation to TRC105.
Results and Conclusion
Irradiation of pressed, isotopically-enriched 72GeO2 resulted in a production yield for 72As of 17 ± 2 mCi/(”A·hr·g) and for 71As of 0.37 ± 0.04 mCi/(”A·hr·g), which are 64 % and 33 %, of those predicted from literature6, respectively. However, these production yields are in agreement with those scaled from observed production yields using analagous natGeO2 targets. The end-of-bombardment 72As radionuclidic purity can be improved by minimizing the 72Ge(p,2n)71As reaction by degrading the beam energy. A 125 ”m Nb containment foil would degrade impinging protons to 14.1 MeV and is predicted to reduce 71As yield by a factor of three, while only reducing 72As yield by 1 %6, improving end-of-bombardment radionuclidic purity from 98 % to greater than 99 %.
Overall decay-corrected radiochemical yield of the 72As isolation procedure from 72GeO2 were 51 ± 2 % (n = 3) in agreement with those observed with natGeO2 57 ± 7 % (n = 14). The beam current was limited to 3 ”A as higher cur-rents 4â5 ”A exhibited inconsistent dissolution and reprecipitation steps, resulting in an overall yield of 44 ± 21 % (n = 6). Dissolution time also played an important role in overall yield with at least one hour necessary to minimize losses in these first two steps. The separation procedure effectively removed all radiochemical contaminants and resulted in 72As(OH)3 isolated in a small volume, pH~4.5 water solution. Over the course of minutes to hours after back extraction, rapid auto-oxidation to 72AsO4H3 was observed. The bulk 72GeO2 target material, which was reclaimed from the isolation procedure, is being collected for future use.
The synthesis of a targeted PET/MRI agent based on the functionalization of 72As-SPION has proved to be a difficult task. Experiments conjugating 72As-SPION to TRC105 through a PEG linker were unsuccessful, despite the investigation of a variety bioconjugation procedures. Current work is investigating the use of SPION@HMSN, which have a similar affinity for 72As as unencapsulated SPION. This new class of 72As-labeled SPION@HMSN has a hollow cavity for potential anti-cancer drug loading, as well as the mesoporous silica surface, which may facilitate the efficient conjugation of TRC105 using a well-developed bioconjugation technique.
In summary, radioarsenic holds potential in the field of diagnostic and therapeutic nuclear medicine. However, this potential remains locked behind challenges related to its production and useful in vivo targeting. The present work strives to address several of these challenges through the use of enriched 72GeO2 target material, a chemical isolation procedure that reclaims the bulk of the target material, and the investigation of new targeted nanoparticle-based PET/MRI agents
Thomson spectrometer-microchannel plate assembly calibration for MeV-range positive and negative ions, and neutral atoms
Production of [11C]cyanide for the synthesis of indole-3-[1-11C]acetic acid and PET imaging of auxin transport in living plants: Production of [11C]cyanide for the synthesis of indole-3-[1-11C]acetic acid and PET imaging of auxin transport in living plants
Introduction
Since its development by Al Wolf and colleagues in the 1970s1, [11C]cyanide has been a useful synthon for a wide variety of reactions, most notably those producing [1-11C]-labeled amino acids2. However, despite its position as rote gas-phase product, the catalytic synthesis is difficult to optimize and often only perfunctorily dis-cussed in the radiochemical literature. Recently, [11C]CNâ has been used in the synthesis of indole-3-[1-11C]acetic acid ([11C]IAA), the principal phytohormone responsible for a wide variety of growth and development functions in plants3. The University of Wisconsin has expertise in cyclotron production and radiochemistry of 11C and previous experience in the PET imaging of plants4,5. In this abstract, we present work on optimizing [11C]CNâ production for the synthesis of [11C]IAA and the PET imaging of auxin transport in living plants.
Material and Methods
[11C]CH4 was produced by irradiating 270 psi of 90% N2, 10% H2 with 30 ”A of 16.1 MeV protons from a GE PETtrace cyclotron. After irradiation, the [11C]CH4 was converted to [11C]CNâ by passing through a quartz tube containing 3.0 g of Pt wire and powder between quartz wool frits inside a 800â1000 ËC Carbolite tube furnace. The constituents and flow rate of the [11C]CH4 carrier gas were varied in an effort to optimize the oven\'s catalytic production of [11C]CNâ from CH4 and NH3. The following conditions were investigated:
i. Directly flowing irradiated target gas versus trapping, purging and releasing [11C]CH4 from a â178 ËC HayeSep D column in He through the Pt furnace.
ii. Varying the amount of anhydrous NH3 (99.995%) mixed with the [11C]CH4 carrier gas prior to the Pt furnace. Amounts varied from zero to 35 % of gas flow.
iii. Varying the purity of the added NH3 gas with the addition of a hydride gas purifier (Entegris model 35KF), reducing O2 and H2O impurities to < 12 ppb.
iv. Varying the flow rate of He gas carrying trapped, purged and released [11C]CH4.
After flowing through the Pt furnace, the gas stream was bubbled through 300 ”L of DMSO containing IAA precursor gramine (1 mg), then passed through a 60Ă5 cm column containing ascarite to absorb [11C]CO2, followed by a â178ËC Porapak Q column to trap [11C]CH4 and [11C]CO.
After bubbling, the DMSO/gramine vial was heated to 140 ËC to react the gramine with [11C]CNâ, forming the intermediate indole-3-[1-11C]acetonitrile ([11C]IAN), which was subsequently purified by solid phase extraction (SPE). The reaction mixture was diluted into 20 mL water and loaded onto a Waters Sep-Pak light C18 cartridge, followed by rinsing with 5 mL of 0.1% HCl : acetonitrile (99 : 1) and 10 mL of the same mixture in ratio 95 : 5, and finally eluted with 0.5 mL of diethyl ether. The ether was subsequently evaporated under argon flow, followed by the hydrolysis of [11C]IAN to [11C]IAA with the addition of 300 ”L 1 M NaOH and heating to 140 ËC for 5 minutes. After hydrolysis, the solution was neutralized with 300 ”L 1 M HCl and purified using preparative high-performance liquid chromatography (HPLC) using a Phenomenex Luna C18 (10ÎŒ, 250Ă10mm) column with a mobile phase acetonitrile : 0.1% formic acid in H2O (35 : 65) at flow rate of 3 mL/min. The [11C]IAA peak, eluting at 12 minutes, was collected and rotary evaporated to dryness, then again after the addition of 5 mL acetonitrile, followed by its reconstitution in 50 ”L of water. Analytical HPLC was performed on the [11C]IAA before and after this evaporation procedure using a Phenomenex Kinetex C18 (2.6ÎŒ, 75Ă 4.6 mm) column with a linear gradient elution over 20 minutes of 10 : 90â30 : 70 (acetonitrile : 0.1% formic acid) at a 1 mL/min flow rate, eluting at 7.6 minutes.
The transport of [11C]IAA was monitored following administration through the severed petiole of rapid cycling Brassica oleracea (rcBo) using a Siemens microPET P4 scanner. Transport was compared following administration to the first true leaf versus the final fully formed leaf in plants with and without exposure to the polar auxin transport inhibitor naphthylphthalamic acid (NPA).
Results and Conclusion
Optimization of the [11C]CNâ gas phase chemistry was performed using two key metrics for measuring conversion yield. First is the fraction of total produced radioactivity that trapped in the DMSO/gramine solution (denoted %DMSO), and second, the fraction of DMSO/gramine-trapped activity that was able to react with gramine to form [11C]IAN (denoted %CNâ). Under certain conditions, the former of these metrics experienced significant losses due to unconverted [11C]CH4 or through combustion, forming [11C]CO2 or [11C]CO. The latter metric experienced losses due to production of incomplete oxidation products of the CH4-NH3 reaction, such as methylamine. Total [11C]CH4 to [11C]CNâ con-version yields is reported by the product of the two metrics. It was initially hypothesized that the irradiation of a 90% N2, 10% H2 target gas would produce sufficient in-target-hot-atom-produced NH3 to convert [11C]CH4 to [11C]CNâ in the Pt furnace. However, conversion yields were found to be low and highly variable, with 13 ± 8 % trapping in DMSO/gramine, 9 ± 9 % of which reacted as CNâ (n = 15). While in disagreement with previous reports1, this is likely as a result the batch irradiation conditions resulting ammonia losses in the target chamber and along the tubing walls. Yields and reproducibility were improved when combining the target gas with a stream of anhydrous NH3 gas flow with conversion yields reported in TABLE 1. However, these yields remained undesirably low, potentially as a result of the 10% H2 carrier gas having an adverse effect on the oxidative conversion of [11C]CH4 to [11C]CNâ. To remedy this, the irradiated target gas was trapped, purged, released in He and combined with NH3 gas before flowing through the Pt furnace. Initial experiments using 99.995% anhydrous NH3 gas resulted in very poor (< 0.1%) [11C]CNâ yields as a result of nearly quantitative combustion forming [11C]CO2. Installation of a hydride gas purifier to reduce O2 and H2O impurities in NH3 improved yields for CH4 in He, but did not significantly affect those from [11C]CH4 in N2/H2 target gas. In disagreement with previous reports2, conversion yields were found to be highly sensitive to overall carrier gas flow rate, with lower flow rates giving the best yields, as shown in TABLE 1. Optimization experiments are continuing.
The total decay-corrected yield for the 1 hour synthesis of [11C]IAA in 50 ”L of water is 2.3 ± 0.7 %, based on the total produced [11C]CH4 with a specific activity ranging from 1â100 GBq/”mol. The principal radiochemical impurity was determined to be indole-3-carboxylic acid. The SPE procedure isolating the [11C]IAN intermediate product was optimized to minimize this impurity in the final sample.
After a rapid distribution of the administered [11C]IAA through the cut petiole and throughout the rcBO plant, upward vascular transport of auxin and downward polar auxin transport was visualized through time-activity curves (TACs) of regions of interest along the shoot. Comparison of these TACS with and without exposure to NPA yields insight into the fundamental physiological process of polar auxin transport in plants.
In conclusion, the Pt-catalyzed oxidative conversion of [11C]CH4 and NH3 to [11C]CNâ is a challenging process to optimize and highly sensitive to carrier gas composition and flow rate. Optimization for our experimental conditions yielded several results which disagreed with previous reports. [11C]IAA produced using [11C]CNâ is well suited for PET imaging of polar auxin transport in living plants
Simplified targetry and separation chemistry for 68Ge production
Introduction
68Ge (tÂœ = 270.8 d, 100% EC) is an important radionuclide for two reasons: 1) once in equilib-rium with its daughter nuclide 68Ga (tÂœ = 68 min, 89 % ÎČ+, 3 % 1077 keV Îł), it can be used as a positron source for attenuation correction and calibration of PET/MRI scanners; and 2) it can be employed as a generator of 68Ga for radiophar-maceutical preparation. Most isotope production facilities produce it using natural gallium (60.1% 69Ga, 39.9% 71Ga, melting point: 39 °C) as target material for proton bombardment at energies > 11.5 MeV, the threshold energy for 69Ga(p,2n)68Ge [1]. A maximum cross section of ~330 mb for natGa(p,x)68Ge occurs at ~20 MeV [1], hence proton energies in this neighborhood are mandatory for large scale production. Galli-um targetry is challenging due to its low melting point and corrosivity, hence compounds such as Ga2O3 (melting point: 1900 °C) or GaxNiy alloys (melting points > 800 °C) [2], have been used as target compounds [3,4,5]. The separation chem-istry technique employed by large-scale produc-tion facilities is liquid-liquid extraction using CCl4 [6,7]. In this work, two simple methods for GaxNiy alloy preparation are presented as well as a simple germanium separation procedure using a commercially available extraction resin.
Material and Methods
GaxNiy alloys were prepared by two methods (A,B). A) electrodeposition over 1.3 cm2 of a gold disk substrate. Ga2O3 and NiSO4.6H2O were dis-solved in a mixture of (27%) H2SO4 and NH4OH at pH 1.5 in a 3:2 mass ratio so that the Ga:Ni molar ratio was 4:1. The solution was then transferred to a 15 mL plating cell, in which a current of 29 mA/cm2 was applied with a platinum anode at 1 cm from the gold surface. B) Ga pellets were fused together with Ni powder at different Ga:Ni molar ratios using an induction furnace (EIA Power Cube 45/900). The resulting alloy pellets were then rolled to foils using a jewelerâs mill pressed between Nb foils to avoid contamination.
Target irradiations were performed on a GE PETtrace at 16 MeV protons. The electroplated alloys were mounted on a custom-made solid target irradiation system with direct water-jet cooling applied to the backside of the gold disk. The alloy foils were placed on top of in a 1.2 cm diameter, 406 ÎŒm deep pocket made of Nb and sealed against a 51 ÎŒm Nb foil using a teflon O-ring. The alloys were in direct contact with the Nb foil to allow thermal conduction. At the rear of the Nb pocket is a water-cooling stream to transfer heat convectively during irradiation.
Ge separation was achieved based on the difference in distribution coefficients between Ge, Ga, Zn, Cu, Ni and Co at different HNO3 molarities in DGA resin (Triskem International). Initial tests on the resin were performed after two pilot irradiations on natural gallium (a,b). a) 16 MeV protons were directed downward on an external beam-line (â30 °) onto 640 mg of molten elemental natGa pooled on a water-cooled niobium support. b) 330 mg natGa pellet was melted in the same Nb pocket well used with the alloys and was also sealed against a 51 ÎŒm Nb foil. The irradiated gallium was left to decay for 2 weeks and then was dissolved in 6 mL of concentrated HNO3. The solution was then passed through 200 mg of DGA resin packed in a 5 mm diameter column at a flow rate of 1.1 mL/min. A separation profile for Ge, Ga and Zn was obtained by collecting 0.2â1.0 mL fractions, which were analyzed by gamma ray spectroscopy on a HPGe detector.
Two thick NiGa4 foils have been irradiated, one for 69Ge production and for radiocobalt, from 58Ni(p,α), separation quantification; and the other one for 68Ge production with the idea of preparing a mini-generator (< 13 MBq) of 68Ga for local use in phantom imaging work and animal studies.
Results and Conclusion
A) Each electroplating batch consisted of 66.5 ± 2.9 mg of Ga2O3 mixed with 44.9 ± 3.6 mg of NiSO4.6H2O (n = 9) in the 15 mL plating cell. Higher concentrations resulted in inefficient electroplating yields due to precipitation. 66 ±
6 % of the total Ga+Ni mass in solution, that is 39.5 ± 3.3 mg of Ga-Ni was deposited after 3 d. Three plating batches over one disk resulted in a maximum target thickness of 86.7 mg/cm2. A fourth batch did not add any significant amount of alloy and salt precipitation became a problem. The electroplated surface looked homogeneous at 10Ă magnification on a microscope and the targets were able to withstand up to 30 ÎŒA without presenting any dark spots.
B) Alloys with Ga:Ni molar ratios of 1.0, 2.0, 2.9, 3.7 and 5.2 were fused by induction heating. TABLE 1 summarizes the results from manipulating these foils. These alloys were analyzed by X-ray fluorescence using a 109Cd excitation source quantifying the x-rays peaks: 9.26 keV for Ga and 7.48 keV for Ni. A linear relationship between the ratio of count rates of these two peaks to the alloy Ga:Ni molar ratio was found and employed for the characterization of the electroplated Ga-Ni layers.
Results from the irradiations over natGa on Nb supports are presented in TABLE 2.
TABLE 3 presents the results from irradiating two thick NiGa4 foils made by induction heating.
Figure 1 contains the separation profile with DGA. 91% of the 68Ge is eluted in 2 mL of de-ionized water.
We developed two simple methods for NiGa4 alloy manufacture. With a melting point > 800 °C and 80% presence of natGa, it is a more convenient target for 68Ge production compared to Ga encapsulated in Nb. The separation method based on the extraction resin DGA yields similar results as the liquid-liquid extraction method mentioned in [6,7], but we believe this is a more convenient method since it only requires a single trap-and-release step and not many extraction steps
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