Introduction Nitrogen [13N] NH3 is a liquid radioisotope, produced by medical cyclotrons for nuclear medicine application and widely applied for evaluation of myocardial perfusion in clinical assessments [1,2]. Owing to its short half-life (10 minutes), the unloading procedure of the radio-active solution of [13N]NH3 from the target is crucial in saving the activity produced for patient. Therefore, an efficient technique in un-loading the radioactive solution from the target body was developed using COMSOL Multiphysics. The new design of the target with improved unloading technique resulted in 30% increase of the available 13N activity. In our experiments, 13N was produced by the 16O(p,α)13N reaction. The energy of proton beam was 16.5 MeV. Material and Methods A 2D model was developed using COMSOL Multiphysics to simulate the inner geometry of [13N] Ammonia target. In the 2D model, water and aluminum were used as materials for the inner body and outer boundary (walls), respectively. The physical equations used to solve the problem of allocating proper place for the loading/unloading opening is turbulent, k-ε Module being extracted from fluid flow module. FIGURE 1 shows the result of simulating water flow on the target water channels. The entrance of the pushing solution (for unloading) was designed to create a turbulent flow inside the target body and, hence, to collect most of the activity inside the target. FIGURE 2 shows the setup for 13N production. A peristaltic pump is used to push the solution after irradiation to the hotcell at 6 ml/min flowrate. The distance from the target to the hotcell is approximately 30 meters. Results and Conclusion FIGURE 3 presents activity produced in milicurie (mCi) for several patient runs. The activity obtained in some experiments reached up to 330 mCi when we irradiated the target with 25 μA for 15 min. This was satisfactory for delivery to the patient at the nuclear medicine department. Moreover, purity of [13N] purity was above 95 % what meets the standard regulation for administration to a patient.

Cyclotron production of 99mTc through the 100Mo(p,2n)99mTc reaction1 is being actively investigated as an alternative to reactor-based approaches. A challenge facing cyclotron pro-duction of clinical-quality 99mTc is that proton bombardment of Mo targets results in production of a number of additional Tc and non-Tc isotopes through various reaction channels.2,3 While non-Tc products can be chemically re-moved, other Tc radioisotopes cannot and will therefore degrade radionuclidic purity and contribute to patient radiation dose.5 The radionuclidic purity of cyclotron-produced 99mTc depends on the nuclear cross section governing each reaction channel, the proton current and energy distribution, duration of bombardment, target thickness and isotopic composition. Although conditions that minimize dose from radioactive Tc impurities have been identified,5 cyclotron performance and thus irradiation conditions may randomly fluctuate between and/or during production runs. Fluctuations of certain parameters, for example the total number of bombarding protons, are expected to have little influence on radionuclidic purity, whereas fluctuations in beam energy, target thickness and isotopic composition may dramatically affect the relative amounts of 93gTc, 94gTc, 95gTc, and 96gTc impurities. It is critical to quantify relationships between potential fluctuations and the reproducibility and consistency of the radionuclidic purity of cyclotron-produced 99mTc to guide development and optimization of target preparation, irradiation, and processing techniques. The purpose of this work is to present a mathematical formalism for quantifying the relation-ship between random fluctuations in Mo target thickness and variability of proton-induced nuclear reaction rates for enriched Mo targets. In this study, we use 96gTc as an example of impurity which can potentially contribute to increased patient dose for patients injected with cyclotron-produced 99mTc.4 Herein, we apply the developed formalism to both the 96Mo(p,n)96gTc and the 100Mo(p,2n)99mTc reaction channels, however, the same approach can be applied to any reaction channel of interest.

One of the most common PET isotopes, 18F, is mainly produced in liquid targets. The production yield depends linearly on the proton beam current used. However, for a fixed proton-beam energy increasing the current of the proton beam results in depositing increasing amounts of heat into the enclosed water target chamber and eventually in its failure. Hence, understanding the thermodynamics of a water target chamber could lead to a target optimization, removing the maximum amount of heat to balance the pressure, increasing the yield and guaranteeing the stability and durability of the system. Work in modeling the thermodynamic processes in a liquid target has also been per-formed by other groups [1-3] and others such as Steinbach [4] have performed analytical analyses of thermal behavior.

Introduction Technetium-99m, supplied in the form of 99Mo/99mTc generators, is the most widely used radioisotope for nuclear medical imaging. The parent isotope 99Mo is currently produced in nuclear reactors. Recent disruptions in the 99Mo supply chain [1] prompted the development of methods for the direct accelerator-based production of 99mTc. Our approach involves the 100Mo(p,2n)99mTc reaction on isotopically enriched molybdenum using small medical cyclotrons (Ep ≤ 20 MeV), which is a viable method for the production of clinically useful quantities of 99mTc [2]. Multi-Curie production of 99mTc requires a 100Mo target capable of dissipating high beam intensities [3]. We have reported the fabrication of 100Mo targets of both small and large area tar-gets by electrophoretic deposition and subsequent sintering [4]. As part of our efforts to further enhance the performance of molybdenum targets at high beam currents, we have developed a novel target system (initially de-signed for the GE PETtrace cyclotron) based on a pressed and sintered 100Mo plate brazed onto a dispersion-strengthened copper backing. Materials and Methods In the first step, a molybdenum plate is produced similarly to the method described in [5] by compacting approximately 1.5 g of commercially available 100Mo powder using a cylindrical tool of 20 mm diameter. A pressure between 25 kN/cm2 and 250 kN/cm2 is applied by means of a hydraulic press. The pressed molybdenum plate is then sintered in a reducing atmosphere (Ar/2% H2) at 1,700 oC for five hours. The resulting 100Mo plates have about 90–95 % of the molybdenum bulk density. The 100Mo plate is furnace brazed at ~750 oC onto a backing manufactured from a disperse on strengthened copper composite (e.g. Glidcop AL-15) using a high temperature silver-copper brazing filler. This process yields a unique, mechanically and thermally robust target system for high beam power irradiation. Irradiations were performed on the GE PETtrace cyclotrons at LHRI and CPDC with 16.5 MeV protons and beam currents ≥ 100 µA. Targets were visually inspected after a 6 hour, 130 µA bombardment (2.73 kW/cm2, average) and were found fully intact. Up to 4.7 Ci of 99mTc have been produced to date. The saturated production yield remained constant between 2 hour and 6 hour irradiations. Results and Conclusion These results demonstrate that our brazed tar-get assembly can withstand high beam intensities for long irradiations without deterioration. Efforts are currently underway to determine maximum performance parameters.

Introduction Radioisotopes of bromine are of special interest for nuclear medical applications. The positron emitting isotopes 75Br (T½ = 1.6 h; β+ = 75.5 %) and 76Br (T½ = 16.2 h; β+ = 57 %) have suitable decay properties for molecular imaging with PET, while the Auger electron emitters 77Br (T½ = 57.0 h) and 80mBr (T½ = 4.4 h) as well as the β−-emitter 82Br (T½ = 35.3 h) are useful for internal radiotherapy. 77Br is additionally suited for SPECT. The isotopes 75Br, 76Br and 77Br are usually produced at a cyclotron either by 3He and α-particle induced reactions on natural arsenic or by proton and deuteron induced reactions on enriched selenium isotopes [1]. As target mate-rials for the latter two reactions, earlier ele-mental selenium [2] and selenides of Cu, Ag, Mn, Mo, Cr, Ti, Pb and Sn were investigated [cf. 3–7]. Besides several wet chemical separation techniques the dry distillation of bromine from the irradiated targets was investigated, too [cf. 2, 4, 5]. However, the method needs further development. Nickel selenide was investigated as a promising target to withstand high beam currents, and the dry distillation technique for the isolation of n.c.a. radiobromine from the target was optimized. Material and Methods Crystalline Nickel-(II) selenide (0.3–0.5 g) was melted into a 0.5 mm deep cavity of a 1 mm thick Ni plate covered with a Ni grid. NiSe has a melting point of 959 °C. For development of targeting and the chemical separation, natural target material was used. Irradiations of NiSe were usually performed with protons of 17 MeV using a slanting water cooled target holder at the cyclotron BC1710 [8]. For radiochemical studies a beam current of 3 µA and a beam time of about 1 h were appropriate. To separate the produced no-carrier-added (n.c.a.) radiobromine from the target material a dry distillation method was chosen. The apparatus was developed on the basis of a dry distillation method for iodine [cf. 9,10] and optimized to obtain the bromine as n.c.a. [*Br]bromide in a small volume of sodium hydroxide solution. Changing different components of the apparatus, the dead volume could be minimized and an almost constant argon flow as carrier medium was realized. Various capillaries of platinum, stainless steel and quartz glass with different diameters and lengths were tested to trap the radiobromine. Results and Conclusion Nickel selenide proved successful as target material for the production of radiobromine by proton irradiation with 17 MeV protons. The target was tested so far only at beam currents up to 10 µA, but further investigations are ongoing. The optimized dry distillation procedure allows trapping of 80–90 % of the produced radiobromine in a capillary. For this purpose quartz glass capillaries proved to be most suitable. After rinsing the capillary with 0.1 M NaOH solution the activity can be nearly completely obtained in less than 100 µL solution as [*Br]bromide immediately useable for radiosynthesis. So, the overall separation yield was estimated to 81 ± 5 %. The radionuclidic composition and activity of the separated radiobromide was measured by γ-ray spectrometry. Due to the use of natural selenium the determination of the isotopic purity was not meaningful, but it could be shown that the radiobromine was free from other radioisotopes co-produced in the target material and the backing. The radiochemical purity as well as the specific activity were determined by radio ionchromatography. Further experiments using NiSe produced from nickel and enriched selenium are to be per-formed. The isotopic purity of the produced respective radiobromide, the production yield at high beam currents and the reusability of the target material have to be studied.

Introduction Temperature modeling using Finite Element Analysis (FEA) is widely used by particle beam-line designers as a useful tool to determine the thermal performance of an irradiated target system. A comparison study was performed between FEA calculated temperatures on platinum with experimental results using direct thermocouple measurements. The aims are to determine the best beam model for future solid target design, determine the maximum target current for different target materials and the temperature tolerance for any modification to our existing solid targetry system. Material and Methods The theoretical temperature of the target sys-tem was determined using SolidWorks 2013 with Flow Simulation Analysis (FSA) module. The FSA module determines the maximum temperature inside the target material given the global conditions (material specification, flow rates, boundary conditions, etc.) for a given target current. The proton beam was modeled as a volumetric heat source inside the target material based on the distribution of energy loss in the material along the beam axis. The method used by Comor, et al1 was used in this study. The method segmented the target material into five individual layers, each layer being 50 m thick. The energy lost per layer was calculated using SRIM3 and converted into the power lost per layer. A thickness of 250 μm of platinum completely stops the impinging proton beam at 11.5 MeV with the highest deposition of power per layer corresponding to the Bragg peak. The target material used in the simulation reflects the physical target disk used for temperature measurements (platinum, dia. 25.0 mm, thickness 2.0 mm) with two K-type thermocouples (dia. 0.5 mm, stainless steel sheath) embedded in the platinum disk. One thermocouple is located in the geometric center, while the other is located at a radial position 8 mm from center. The outer thermocouple is to determine the peripheral temperature near the o-ring seal. Temperature was maintained below the melting point for the material (Viton®, melting point 220 °C) during the irradiation to ensure the integrity of the water cooling system. The solid targetry system used in this study is an in-house built, significantly modified version2 of a published design1. The solid target system is mounted onto an 18/18MeV IBA Cyclotron with dual ion source, on a 300mm beam-line with no internal optics or steering magnets. A graphite collimator reduces the beam to 10mm in diameter and a degrader is used to reduce the proton beam energy to 11.5 MeV, considered suitable for production of radiometal PET isotopes 89Zr and 64Cu. Temperature was measured with and without the 300 mm beam-line to compare the effects of beam divergence on the solid target (FIGS. 1 and 2). The experiment was conducted using both H− ion sources with different ion-to-puller extraction gaps (ion source 1 is 1.55 mm with ion source 2 at 1.90 mm). The setting of the ion-to-puller gap changes the focusing of the accelerated beam inside the cavity. Results and Discussion The segmented beam model was used to calculate the temperature on and within the target, as well as the maximum temperature of the bulk material. The first segment is the leading segment of the material irradiated by the incident proton beam. Results are shown in TABLE 2. Target temperatures were measured experimentally under two different conditions; target attached at the end of a 300mm beam-line and target attached directly to the cyclotron. The temperature was measured experimentally using the platinum disk with 2 thermocouples inside the bulk target material irradiated on the end of a 300mm beam-line. The measured temperature is shown in TABLE 2. The variation between ion source 1 and 2 for the temperature measured in the center was 11–15 %, while the variation on the radial position was 2–6 %. A smaller ion-to-puller extraction distance (ion source 1) reduces the cross-sectional area of the accelerated beam; the consequent high proton current density (10mm diameter collimated beam) increases the temperature inside the bulk material for a fixed target current. The highest observed radial temperature was 93 °C, with target current of 50 μA using ion source 1. This is well below the melting point for the o-ring seal. The temperature measured experimentally using the same platinum disk with no beam-line is shown in TABLE 4. A temperature difference of up to 7 % was measured between ion source 1 and 2 at the exit port without the beam-line, while the maximum variation on the radial position was 3 %. A comparison between the calculated theoretical and measured temperatures is shown in FIGS. 3 to 6. The temperatures calculated by the FEA model underestimate the temperature regardless of target position (with or without the beam-line) and for both ion sources. The temperature difference between the FEA model and the experimental results increases with increasing target currents. As shown in Figure 3, at the target center the FEA model underestimated the temperature by 22–32 % for ion source 1 and 13–22 % for ion source 2. This is consistent with the difference between the two ion sources due to the difference in the ion-to-puller gap size. With the target mounted at the exit port the theoretical and measured temperature for the center of the platinum disk is shown in FIGURE 4. The FEA model underestimates the temperature at the center of the platinum disc by 2–10 % for both ion sources. As shown with the previous experiment, the margin of error increases with increasing target current. Comparison between FIGS. 3 and 4 shows the measured temperature at the center of the platinum disk is significantly lower when the target is attached to exit port of the cyclotron. Localised area of high current density (hot spots) is not registered as higher temperature in the bulk material. True temperature inside the bulk material is highly dependent on the thermal conductivity of the target material and the resolution of the thermocouple. The cross-sectional area of the beam ‘hot-spot’ will be greater due to beam divergence at the end of the beam line compared with the exit port. The ‘hot’ area of the expanded beam becomes a significant portion of the overall collimated beam (collimator dia. 10.0 mm). A more uniform beam profile (less heterogeneity) evenly distributed the area of high current density across the disk surface, effectively increasing the temperature of the bulk material while decreasing the sensitivity required to measure the true temperature. As observed from this comparative study it appears that a more homogeneous current density leads to a higher temperature measurement at the target center. With the solid target at the end of the beam-line, target current lost on the collimator and beam-line was >55%. The effect of beam divergence is clearly observed in TABLE 5. With the target mounted directly at the exit port the current lost was reduced to < 40 %. Although the average proton current density is the same for any set target current, irrespective of target position, the contribution of the peripheral beam to the total target current should not be underestimated. A loss of ~40 μA on the collimator and beam-line places greater reliance on the center of the ‘hot’ beam to maintain the same target current. The temperature at the radial position (FIG. 5) observes the same trend as for the temperature measured in the center. The error increases for higher target currents and the FEA model underestimated the temperature by 19–40 %. The error at this location is due partly to the model’s assumption of a uniform heat source, applied to the material on a single axis (perpendicular to the material surface) and does not account for any scattering or divergence of the incident proton beam. FIGURE 6 shows that the FEA model underestimated the radial temperature by 16–37 %, when the target is connected to the exit port, for reasons discussed previously. Comparison with FIG. 5 (target on the beam-line) shows the same margin of error between the FEA and the experimental results (19–40 %). The temperature difference between the FEA model and measured temperature at the radial position is independent of the beam profile and beam divergence. The FEA model underestimated the temperature at the radial location with or without the beam-line and for both ion sources. The significance difference in temperature between the FEA model and the experimental is due to our model assumption that the maximum radial temperature is on the irradiated surface and not inside the material corresponding to the layer with the maximum energy lost. In addition, the FEA model does not ac-count for the divergence of the proton beam as it travels through the material. Given the temperature at 50 μA target current is > 90 °C (TABLES 3 and 4) we have capped the experi-ment below this point to prevent any damage the o-ring seal. Conclusion The segmented FEA model was inadequate in determining the temperature for the target at the end of a 300mm beam-line (> 30 % difference). A combination of beam divergence and greater uniform coverage of high current density beam resulted in a higher than predicted temperature reading. However, the segmented FEA model provides a good estimation (< 10 % difference) for the observed temperature of the bulk material at the exit port. The simplistic FEA model was unable estimate the temperature at the radial position (~ 40 % difference) regardless of ion source or target position. A comparison between the two ion sources with different ion-to-puller extraction gap, leading to different focusing of the accelerated beam yield minimal temperature difference. Although a 15% difference was observed between the ion sources at the end of the beam-line, a major contributing factor is beam divergence beyond the magnetic field rather than the beam size of the accelerated beam. Further studies are underway to determine the beam profile (quantitatively using radiographic film), quantify the contribution of the peripheral beam to the total beam current by comparing different size collimators and to investigate other FEA models by applying different beam models (heterogeneous and homogeneous beam) and different heat sources (surface vs. volumetric). Currently the RAPID Lab solid targetry is placed at the end of the beam-line for easy loading and unloading, since multiple target irradiations are performed per month2. However, RAPID is presently developing a new solid targetry sys-tem which eliminates the need for a beam-line and will be able to manage a maximum extracted target current of 150 μA.

Introduction The expansion of our PET isotope production with a new TR-19 cyclotron necessitated a suitable solid target transport system. None of the known existing and proposed solid target transport systems (STTS) was able to meet the technical and budget requirements of the MIR cyclotron facility [5]. A unique carrier design allowed us to develop a fully automated 50.8 mm inner diameter pneumatic tube STTS with an in-hot-cell compact form factor receiving station. The cyclotron or vault side loading station is a mere vertically symmetric version of the in-hot-cell station. The carrier is able to accommodate any of our inhouse developed 86Y, 64Cu, 76Br, 89Zr and 99mTc target holders without further modifications. Material and Methods Technical constraints were imposed by the dimensions of the target holders (FIG. 1) and the overall station size (FIG. 3). A receiving station would be inside a hot cell and, up to three sending stations would be located in the confined vault space under the solid target irradiation units. In addition, safety and budget requirements demanded a fully automated, easy to maintain STTS. The target holders are of various geometries with the 99mTc having the maximum dimension of 46.65 mm along its diagonal. Pseudo carriers with diameters ranging from 41 to 49.5 mm (no wear band) and lengths from 50.8 to 102 mm were tested on 50.8 mm inner diameter Kuriyama Tigerflex™ and Goodyear Nutriflex™ tubing. Smaller diameter and length test samples became wobbly, slow, and were getting stuck on occasion. Lengths in the upper limits became stuck in turns with radii close to the minimum radius of the tubing. The necessary negative pressure was achieved by employing a 2.5pHP Ridgid WD06250 blower. The transparent Goodyear Nutriflex™ tubing was chosen for the further STTS development. A carrier capable of loading and unloading regardless of its axial orientation was constructed. This novel design allows for a relatively compact station W 112 × H 220 × L 300, which reduce the dependence on the location of the tube openings in the walls of the hot cell (BqSv, Taiwan). As a result the station can be conveniently placed in areas not typically occupied by processing modules or used by chemists, e.g. close to the upper left corner. To avoid reliance on expensive proprietary parts, all components were designed or chosen to insure reliability with minimal maintenance. The enclosure and opening mechanism are 3D-printable using ABS plastic, and can be made in-house on demand. “Platform sharing” between hot cell and vault stations further simplifies support and maintenance. As with the mechanical hardware, the electronic components and boards were selected to minimize the dependency on a single supplier. The main controller board is based on Atmel\'s AVR series of microcontrollers, which are known to be largely backward compatible, well documented and have an extensive user support base. A single “brick” controls up to three stations. Bricks can be daisy chained with one functioning as a master. The control software takes advantage of the rapid development capabilities of National Instrument\'s LabView graphical language. It is intended to work on Unix-like and Windows operating systems as well as to allow control from hand-held devices. Password security, interlocks and traceability follow the accepted safety standards for radioisotope handling. Results and Conclusion The Symmetric STTS has proven characteristics of reliability, ease of use and safety over hundreds of runs. Given that no convenient carting path exists, it is the ideal means for bringing solid target holders from the underground cyclotron vault to the chemistry processing hot cells at ground level. Transported activities are less than 37.0 GBq (1.0 Ci) for 64Cu and 3.7 GBq (100 mCi) for 89Zr. Carrier velocity is about 4.7m/s minimizing the time activity is present between cyclotron and hot cell. No human interaction with the irradiated target is needed during transport. The carrier does not need to be taken out of the STTS. Even though the BqSv hot cells are equipped with teletongs, they are not needed to recover the target when it arrives at the hot cell; the target is directly dropped into the processing module, e.g. the dissolution vessel for 64Cu processing. The software is engineered in a manner that gives the operator full control of the states of the sending and receiving stations. At the same time, it avoids graphically dense and overloaded GUI in order to reduce the probability of human error. Currently the control program runs on a PC/Laptop and communicates with the controller over USB. LabView provides add-ons that allow control with a tablet or other hand-held (under development). The fully automated symmetric STTS is ideal for isotope production facilities that are being envisioned, conceptualized or are in their planning stage. Its versatility, low initial and operating costs might even justify deployment in facilities which already employ a less optimal solid target transport. Invention application for the Symmetric STTS was filed with the Office of Technology Management of Washington University in Saint Louis, Missouri, USA.

Introduction 100Mo target design is key to commercially viable large scale cyclotron production of 99mTc. The target back plate supporting the 100Mo must be chemically inert to the target dissolution conditions but ideally it should also be able to dissipate the high thermal loads of irradiation, not contaminate target substrate with radionuclidic by-products, and be adequately inexpensive to allow for single use. Aluminum was selected as our target support as it satisfies these requirements. Our process entails rolling 100Mo powder into a foil of desired thickness, and then diffusion bonding [1] the foil onto an aluminum back plate. The 100Mo targets were designed to be 20×80×0.1 mm to match our TR24 cyclotron’s proton beam profile and energy. Efforts are currently underway to scale up the process to allow for simultaneous production of multiple targets at once. Material and Methods The crude enriched 100Mo foil (99.815% enrichment) was made from 100Mo powder using a horizontally mounted rolling mill and an aluminum hopper. The crude foil was rolled repeated-ly, and the space between the rollers gradually reduced until the thickness of the foil was changed from an initial thickness of 0.3 mm to a thickness of 0.1 mm. The rolled 100Mo foil was annealed under reducing atmosphere and then bonded to the aluminum target plate support under inert atmosphere in a heated press at 500 °C. Results and Conclusion By rolling 100Mo foils from powder we were able to produce uniform foils with an average density of > 98 % compared to the maximum theoretical density of 100Mo (n = 5) and thicknesses of roughly 0.1 mm. All foils produced were the desired 20 mm width (i.e. limited by the width of the opening of the hopper) and trimmed to the desired 80 mm length. The annealing process was necessary due to the brittleness of the un-annealed rolled foil and the difference in the thermal expansion coefficients of molybdenum and aluminum which caused un-annealed foils in previous experiments to crack and break off during pressing (n = 10). Surface preparation of the aluminum support plate was also found to play a critical step in the efficiency of the bond, and continuing effort to scale the above de-scribed procedure to mass produce 100Mo tar-gets is ongoing. Targets have undergone preliminary testing to 250 μA.

Introduction The Comecer ALCEO Metal system is intended to be a comprehensive solid targetry system, capable of all steps necessary to produce copper isotopes (60Cu, 61Cu & 64Cu) from enriched nickel: plating, transfer to/from cyclotron, irradiation, and dissolution/purification. To develop plating and chemistry methods, we plate natural nickel, and irradiate with deuterons to produce 61Cu. This alleviates the need for expensive enriched nickel isotopes, but gives a lower activity yield. We report a few issues with the ALCEO system, and some of our modifications. Material and Methods BRIEF DESCRIPTION OF SYSTEM: The ALCEO system uses cylindrical shuttles (dia 28 mm, height 35 mm) comprised of an Al body with a Pt well, onto which the Ni is plated. Shuttles are transferred pneumatically from the hot cell to the irradiation module, on the end of the cyclotron beamline. The plating and dissolution are both done at the electrochemical cell, located in the hot cell. This cell is connected by capillary tubes to the electrolytic solution reservoir (for plating), or the acid reservoir (for dissolution). These tubes form a recirculation loop, through which the fluid is propelled by an inline micropump throughout plating and dissolution. The platinum well is 16 mm in diameter, while an O-ring is used to plate only the center (6 mm in diameter). A constant DC voltage is applied. PLATING: We dissolve natural nickel nitrate (99.999% pure) into an electrolytic solution comprised of deionized water, ammonium hydroxide and ammonium chloride (pH = 9.3). We use 30–100 mg of natNi in a 10mg/mL solution. We have varied the ALCEO electrochemical cell voltage between 2.25–3 VDC, and tried to maintain a low pump flow rate between 1–2 mL/min. The electrochemical cell uses a fixed metal tube as the anode (~3mm above the plating surface). This tube also delivers the electrolytic plating solution to the Pt surface, forming part of the recirculating loop. The Pt surface is in contact with a gold-plated cathode. Due to issues discussed below, we have built a custom plating rig for the ALCEO shuttles, which does not use the pump/recirculation loop, but leaves the reservoir of electrolytic solution in place, atop the plating surface. A graphite rod is used for the anode, rotating offcenter ~2mm above the plating surface. We use the same size O-ring to plate only the center 6 mm of the Pt surface, and apply a constant DC voltage. TRANSFER TO/FROM CYCLOTRON: The pneumatic transfer tube is 50 ft long between the hot cell and the cyclotron vault, and has a rise of 14 ft from under the floor to the ceiling of the cyclotron vault. IRRADIATION: The ALCEO irradiation module holds the plating surface orthogonal to the beam path. The module has a 10-mil-thick (0.010”) Al front foil, supported by a hex-grid. Once we realized the thickness, we replaced this with a 1-mil-thick Al foil, followed by a 1-mil-thick Havar foil. The foil is cooled by a flow of helium, while the shuttle and grid are cooled by a flow of water. The helium and water are cooled in heat ex-changers by chilled water. As initially plumbed, the chilled water flowed through the heat ex-changers in series, cooling the helium first, then the water. After initial runs, we plumbed the heat exchangers in parallel, teeing the chilled water to the supply of each heat exchanger, and teeing the returns together. Irradiation is performed with a PETtrace 800 accelerating deuterons to 8.4 MeV on target. The beam current limit is 20 μA for the ALCEO Metal target. A set point of 19 μA is used to avoid the system tripping off. DISSOLUTION/PURIFICATION: The ALCEO system circulates 5 mL of 6M HCl, while heating the shuttle to 100 ⁰C for 40 min. This solution is loaded onto a column containing 10 g of 200–400 mesh chromatographic resin in chloride form. A separation is performed yielding three solutions: The column is washed with 40 mL of 6M HCl to obtain the Recovered Nickel Solution, then 20 mL of 4M HCl to obtain the Cobalt Solution, then 10 mL of 0.5M HCl to obtain the Cop-per Product Solution. Results and Conclusion PLATING: Using the ALCEO method, the platings obtained had a tendency to mound, (up to 0.75 mm thick for 50 mg) giving a lower density of 3–4 g/cm3. This was attributed to the anode tube being fixed in place over the center of the plating surface. Using the custom rig, almost no mounding was observed, (0.25mm thick for 50 mg) giving a density of 7 g/cm3, closer to nickel’s nominal density of 8.9 g/cm3. FIGS. 1 and 2 attempt to show the mounding from the ALCEO method, and relative flatness from the custom rig. Both methods give a rough, or “fuzzy” plated surface. FIG. 2 shows that the custom rig exaggerates this “fuzziness”. Using the ALCEO method, a slower pump speed (~1 mL/min) gives a smoother plating surface, but the pump has a tendency to lock up at this lower set point, stalling the plating. Using the ALCEO method, slight increases in the voltage (2.65 V instead of 2.25 V), can form thin stalagmites of nickel, electrically connecting the anode and the plating surface, ending the chance for a useable plating. Using the custom rig, no stalagmites are seen, adjusting the voltage from 2.3 to 3.0 V. This leads to the potential for a faster plating. Both the ALCEO method and the custom rig have obtained plating efficiencies of 95 %. TRANSFER TO/FROM CYCLOTRON: The shuttle typically transfers without issue in < 15 seconds. Once or twice it has remained in the transfer tube, but been retrieved by cycling the com-pressed air/vacuum a couple of times. IRRADIATION: During initial testing, the temperature of the return water rose rapidly during irradiation. This was attributed to the chilled water already gaining heat from the helium heat exchanger. Once the parallel chilled water plumbing was implemented, the water temperature rose much more slowly. Initial testing with the 10-mil Al foils gave a very poor activity yield. The 1-mil Al foil ruptured under the 20 psi helium pressure before beam was applied. The 1-mil Havar foil produced 1.57 mCi of 61Cu at EOB, giving an activity yield of 0.308 mCi/μAh (results summarized in TABLE 1). This compares to yields of 1.4 obtained by [1], and 0.29 obtained by [2] for deuterons on natNi. DISSOLUTION/PURIFICATION: The dissolution in 6M HCl is close to 100% efficient by weight. After purification, the three solutions were assayed by dose calibrator as summarized in TABLE 2. The purification is very efficient at removing the starting material, and long-lived Co isotopes from the Copper Product Solution, as seen with the 57-hour EOB measurements. However, much of the desired 61Cu is removed as well, with only 32% remaining in the product. The lack of nuclide impurities in the Copper Product Solution was confirmed by gamma spectroscopy using a HP-Ge detector.

Das Neuroblastom ist der häufigste extrakraniell gelegene solide Tumor der pädiatrischen Onkologie. Der Verlauf der Erkrankung geht von spontaner Regression oder Differenzierung bis hin zu tödlich verlaufenden Erkrankungen. Die Mortalität von Patienten mit Tumoren in fortgeschrittenen Stadien ist immer noch sehr hoch. Die aggressivsten Tumoren sind die, die eine Amplifikation des Protoonkogens MYCN aufweisen. Eine Untergruppe dieser MYCN amplifizierten Tumoren weist eine Coamplifikation von DDX1 auf. Die Prognose dieser Patienten ist besser als die mit allein MYCN amplifizierten Tumoren, wenn auch immer noch schlechter als die von Patienten ohne MYCN Amplifikation. Das DDX1-Protein ist eine putative RNA-Helikase. Über seine genaue Funktion ist noch nicht viel bekannt. Ziel dieser Arbeit war es, potentielle Ziel-mRNAs von DDX1 zu identifizieren, um einen besseren Einblick in die Funktionen von DDX1 und mögliche Wege der Beeinflussung von Tumorverhalten und Prognose zu erhalten. Hierzu wurden eine DDX1 amplifizierte und eine nicht amplifizierte Zelllinie in Kultur genommen und eine Immunopräzipitation mit Zelllysaten der beiden Zelllinien durchgeführt – jeweils mit einem spezifischen Antikörper gegen DDX1 und einem unspezifischen Kontrollantikörper. Die Identifizierung der an DDX1 gebundenen mRNAs erfolgte mittels Microarray. Validiert wurden einige der im Microarray identifizierten RNAs mittels RT-PCR. CDK1, ATM und p18 ließen sich als spezifische Ziel-mRNAs von DDX1 identifizieren.