Qucosa – Hemholtz-Zentrum Dresden-Rossendorf
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Development of radiometal automated laboratory workbench
Full text linkIntroduction
Radiometals are finding more and more applications in molecular imaging and targeted therapy. For PET imaging, all the novel radiometals are directly or indirectly produced on cyclotrons. Key step in their production is achieving proper radionuclidic, radiochemical and chemical purity, as well as high specific activity. Automation of the process enhances reproducibility, shortens necessary operations and decreases radiation burden.
We have, therefore, developed universal radio-metal automated laboratory workbench (RALW) that is focused on separation processes from solid and liquid (solution) targets via solid phase extraction (SPE).
Material and Methods
RALW is versatile platform for separation, formulation and simple labeling processes. The following FIG. 1 displays its basic scheme. RALW´s main parts are: two reactors, two selec-tors, peristaltic pump, 3/2 way valves, and separation column. Prime reactor R1 is designed to carry out several functions. It can transport solid target material from shielding container to process position, or handle liquid target filling. In both cases, the reactor is leakagefree up to 5 bars. There are 4 positions available to bring solvents to the reactor 1 or applying on a SPE column according to the separation sequence with use of peristaltic pump. Smart software allows for collecting defined fractions leaving the column, e.g. enriched target matrix and the desired radionuclide, by monitoring activity profile and controlling the splitting valves. The system also minimizes losses during transport of the solvents/fractions to the reactor R2 and the software also controls final volume settings (activity concentration) of the product. Up to three positions are available for bringing solvents/solutions to the reactor R2 for formulation or simple labeling steps like chelation. The system’s hardware is driven by a PLC and I/O cards. The PLC is placed outside the module to avoid radiation damage. The module, PLC and host PC communicate via an Ethernet cable. This solution significantly reduced number of cables connecting the module with other component in the control chain. The PLC is controlled via host PC equipped with userfriendly interface.
Results and Conclusion
The presented RPLW system is rather versatile tool for separation of metal radionuclides and simple postprocessing (formulation/labelling) of the product in stable environment and easy control mechanisms. The RPLW operating prototype is shown on the FIG. 2
New control systems for aging SIEMENS cyclotrons
Full text linkIntroduction
When properly maintained, cyclotrons often remain in operation for 20 years and more. However, as the years pass the control systems in particular become challenging to support. The I/O cards and other hardware eventually become obsolete, making spare parts difficult or even impossible to find. And the knowledge and ability to reload and configure the software also gets lost as operating systems and media storage technology change. This obsolescence is true of the Siemens RDS-112 cyclotron, which is controlled using a 486 computer, connected to an external STD card rack containing up to 15 I/O cards. These I/O cards were last manufactured in the 1990’s, and the iRMX-based control programs malfunction on computers newer than a 486 processor.
A control system upgrade for the RDS-112 cyclotron has been developed by PET Technical Consulting Inc. This commercially available control system reduces operator training time, requires less maintenance, and supports new targets and custom product processes.
Material and Methods
The availability of high channel count I/O cards, and the decision not to support the old CPCU synthesis units, means the entire STD card rack can be replaced with 5 National Instruments (NI) I/O cards. The replacement computer is an industrial grade rack mounted PC with RAID 1 mirrored pair hard drives in front panel access quick swap bays.
Two NI PCI-6509 Digital I/O cards connect directly to the RDS electronics, channel assignments are mapped using software configuration. Three NI PCI-6229 Multifunction I/O cards connect to the RDS electronics through a cable breakout interface plate, the terminal blocks are wired as needed to map the channels. The new control software was created using National Instruments LabVIEW. The new control sequences have a core based on the original RDS-112 FORTRAN control programs. Then hundreds of improvements were made to simplify operation, increase flexibility, minimize user involvement and mistakes, and clearly display key parameters and fault conditions.
System control has been combined into a comprehensive Graphical User Interface, with controls and indicators grouped together onto subsystem pages. Commands that once needed to be typed-in have been replaced with a clickable control for each function. Bar graphs display target and slit currents. Status is obvious with red faults against normally green indicators. Audio alarms cue the operator for process interaction, warn if target current or pressure drifts from setpoint, or if faults occur with power supplies, vacuum, or water cooling. Improvements in sequences and beam algorithms have reduced the time to achieve full beam on dual targets from 10 minutes down to 3 minutes.
Results and Conclusion
This new control system has been installed on (5) five RDS-112 cyclotrons used for commercial isotope distribution. The total combined operation time of these systems after receiving the upgrade is now over 17 years, during this time the control system operation has been nearly problem free.
UPDATE: The Siemens RDS-111 cyclotron is controlled by a VME computer that is now end-of-life. The VM30 and VM42 CPU boards and many of the I/O modules are no longer manu-factured. PET Technical Consulting is developing a control system replacement for the RDS-111 cyclotron with expected completion in 2014
Theoretical analysis of the effect of target-thickness fluctuations on reaction-rate variability for proton-induced nuclear reactions on enriched Mo targets
Full text linkCyclotron 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
Visual observation of boiling in batch-style water targets
Full text linkIntroduction
Batch-style water targets used for F-18 production are known to operate under boiling conditions in the target irradiation chamber, but the distribution of vapor under steady-state conditions was previously unknown. Thermal performance of batch targets has been correlated to average void in the target [1], but the simplified assumptions of such models do not represent the true non-uniform boiling behavior. Visualization targets can be used to observe boiling inside of a target during operation [2–5].
Commercial BTI targets operate at 28–35 bar (400–500 psi) with heat inputs of 0.5 to 3 kW and fill volumes of 1 to 4 mL. Recently, a visualization target featuring two transparent viewing windows was used to observe boiling conditions for realistic operating beam power, target pressure, and fill volume [4]. The same methodology has been applied to three additional visualization targets to examine the effect of target geometry on observed boiling phenomena.
Material and Methods
The original visualization target featured an aluminum body with a 0.127 mm (0.005 inch) integral aluminum beam window and two viewing windows made of optically clear sapphire (Al2O3). It was operated on an IBA 18/9 cyclotron with 18 MeV protons at beam power up to 1.1 kW, for pressures of 5 to 21 bar (70 to 300 psi), and a fill volume of 2.5 mL.
All of the new designs featured a wider chamber to allow for higher beam transmission and an increased chamber height, consistent with cur-rent trends in high power targets. One target featured a reduced chamber depth, and another had a ramp in the back of the chamber to reduce fill volume. Target pressure was limited to a maximum of 14 bar (200 psi) due to the larger diameter beam window.
A video camera was used to record the boiling conditions observed for each target under several lighting conditions. During irradiation, the proton beam excites the water molecules, producing visible blue light emissions during de-excitation. These light emissions provide a good indication of beam distribution and penetration depth. A strong backlight can be used to produce clearer images of bubbles generated during boiling.
Results and Conclusion
Proton range and visible blue light emissions were recorded in dark ambient conditions. The width of the Bragg peak and natural circulation in the bulk fluid were visible with good ambient lighting. Size and distribution of vapor bubbles could be observed by using a strong backlight. The beam current was increased gradually to determine the thermal limit for each target for several fill volumes and pressures.
Two thermal limits were observed which resulted in some beam penetration in the top region of the beam. For lower fill volumes, steam ac-cumulates in or around the helium overpressure bubble, causing the helium bubble to move into the upper region of the beam. For higher fill volumes, beam penetration occurs due to excessive voiding, when bubbles produced in the beam region cannot rise quickly enough out of the path of the beam
Annual Report 2014 - Institute of Ion Beam Physics and Materials Research
Full text linkThis past year 2014 was the year when we finally completely arrived as a “full member” in the Helmholtz Association. This is related to the successfully passed research evaluation in the framework of the Program Oriented Funding (POF), which will give us a stable and predictable funding for the next five years (2015 – 2019). This is particularly true for our large-scale user facilities, like the Ion Beam Center (IBC) and the electron accelerator ELBE with the free-electron laser. Most of our activities are assigned to the program “From Matter to Materials and Life” within the research area “Matter”, in cooperation with several other German Helmholtz Centers. Our in-house research is performed in three so-called research themes, as depicted in the schematic below. What is missing there for simplicity is a small part of our activities in the program “Nuclear Waste Management and Safety” within the research area “Energy”.
Our research and facilities were well appreciated by the evaluation committee, who made the following judgement about the Ion Beam Center:
“The Ion Beam Centre (IBC) of HZDR is an internationally leading ion-beam facility (with ion energies ranging from several eV to several tens of MeV). At both the national and international level it is one of the key players and is unique in its kind. The synergy between forefront research and user service has been leading to a very good publication output for both in-house research and user research. …
The very broad range of beam energies, the versatility of techniques and applications – both for ion beam modification of materials and for ion-beam analysis – makes the IBC unique in its kind. …
The strength of IBC is that its activities are based on a combination of forefront research and user service, which mutually interact in synergy and strengthen one another. In turn, this synergy has been leading to a very good publication output for both in-house research and user research.”
In order to make our Annual Report a bit more compact, we have decided to include only four full journal papers this year. This was also triggered by the fact that our publication activities have turned out be become more diverse, in more diverse journals than in the past, and often through longer papers, which would be too long to reprint them here. However, apart from the constantly quantitatively high publication output, we succeeded to publish in excellent journals such as Nature Physics, Nano Letters and Physical Review Letters, in fields as diverse as ion beam physics, magnetism and terahertz spectroscopy.
Two of our scientists, Dr. Artur Erbe and Dr. Alexej Pashkin obtained their Habilitation in 2014, both at University of Konstanz. For the first time, we are hosting an Emmy Noether Young Investigator Group funded by the Deutsche Forschungsgemeinschaft (DFG); the group works on the hot topic of magnonics and is headed by Dr. Helmut Schultheiß.
Finally we would like to cordially thank all partners, friends, and organizations who supported our progress in 2014. Special thanks are due to the Executive Board of the Helmholtz-Zentrum Dresden-Rossendorf, the Minister of Science and Arts of the Free State of Saxony, and the Minister of Education and Research of the Federal Government of Germany. Numerous partners from universities, industry and research institutes all around the world contributed essentially, and play a crucial role for the further development of the institute. Last but not least, the directors would like to thank again all IIM staff for their efforts and excellent contributions in 2014
A honeycomb solid target design
Full text linkIntroduction
Solid targets for PET and SPECT radionuclides are getting popular. For radiohalogens the limiting factor, beside the high cost of enriched target material is beam current due to poor heat conductivity of the target material(s). We have designed a honeycomb solid target which has advantages over the traditional circular hole de-sign: 1) Even distribution of target material, 2) it takes higher beam current, 3) less target material loss during distillation (1) and 4) no “creeping” (surface tension phenomena) of the target material during distillation.
Material and Methods
The target (see FIG. 1.) consists of 19 hexagonal 0.3 mm deep openings (see FIG. 2.) thus having 84% transparency/transmission, in a 24×2 mm platinum disk. There is a 10mm circular cavity on the reverse side giving a 200µm thickness of the platinum. The irradiations were performed on an IBA twin 18/18 Cyclon equipped with a Costis sold target system.
The target material thickness was ~300mg/cm2 124TeO2 (> 99.9% I.E., Isoflex) with 5% w/w Al2O3 (99.99%, Sigma-Aldrich). The target was irradiated with 14.8MeV protons (18 MeV degraded by 500µm aluminium).
Results and Conclusion
The target was able to take beam current up to ~35 µA (higher BCs have not yet been investigated); our “traditional” target (10mm circular hole) has a limit of ~ 20 µA. This means that the effective yield is ~ 50 % higher with the honeycomb as compared with the “traditional” target design
“5th generation” high current solid target irradiation system
Full text linkIntroduction
A new high current (up to 50 kW) solid target irradiation system is being built. While retaining the same beam power capability of the previous target generation, the system is a totally new design with many improvements, simplified constriction, more reliable operation and a novel approach to target handling, beam collimation and beam diagnostic.
Unlike the previous, three-part soldered target, the new target is fabricated from a single piece of metal.
Material and Methods
The target (or rather the target-material holder) is a single metal plate (usually copper or silver) incorporating the seals and the cooling channels (FIG. 1). The target is placed in the beam at 7°. Depending on target material and coolant flow the target can handle beam powers up to 50 kW (FIG. 2).
Target transfer (utilizing a special shuttle) is pneumatic. Part of the transfer pipe is shown above the target station.
Except the target o-rings (a part of each target) there are no elastomer seals in the system; all is of soldered/welded construction and metal seals.
Sectional view (FIG. 3.) shows that target in place in the chamber. The target and the chamber are electrically insulated from the rest of the system, thus forming a Faraday cup for accurate current measurement.
The collimator is formed of a two part silver casting. It is designed to handle up to 10 kW of beam power. Four-sector silver mask in front of the collimator allows precise beam cantering.
The collimator parts were cast using 3D printed wax patterns. This allowed to create a complex pattern of cooling channels that are difficult to produce by machining (FIG. 4.)
All the actions of target shuttle landing and the target placing are performed by three air cylinders. All three are fitted with Vespel SP22 (Du Pond) seals.
Unlike previous systems that used mechanical grabbers to manipulate the target, low vacuum is employed to hold the target during removal from the shuttle and placing in the irradiation chamber. This greatly simplifies the operation and is more reliable.
The pneumatic transfer system is using two vacuum producer to transfer the target shuttle between the target station and the hotcell. Both landing terminals in the target station and hotcell, as well as the transfer line itself, are under negative pressure preventing any spread of contamination.
The hotcell landing terminal incorporates a fully automatic target-material dissolution system. After landing, the target is removed from the shuttle and the active face pressed against a reaction vessel where the dissolution takes place (FIG. 5.)
All the functions of target transfer, placing and manipulations are controlled by a simple PLC (FMD88-10 PLC, Triangle Research)
Results and Conclusion
While intended mostly for cladding with metallic target materials, a special version of the target was designed to handle salts or oxides that can be fused and retained in grooves on the target face (FIG. 6.) Despite the poor thermal conduc-tivity of most of those materials, this target can handle high beam currents.
FIGURE 7 shows a thermal modelling of the cen-tral 10×25 mm segment of the target (highest heat flux region under a Gaussian beam). Copper target with rubidium chloride fused in 0.8 mm wide and 1.7 mm deep grooves and spaced by 0.5 mm (60% coverage). Beam of 70 MeV energy and 400 μA intensity is collimated 20 % (320 μA on target). Cooling-water flow is set to 25 l/min.
Cladding the target face with a thin metallic layer can help containing the target material. This process is currently under development.
Most aspects of the system operation and con-striction were successfully used in the previous “generations” of targets in the last 30 years. The new system will provide improved performance with a simpler and more reliable design, lower maintenance and lower consumables cost.
FIGURE 8 shows the “4th generation” system and target (2005). Dozens variants of this design are in use all over the world
Transport system for solid targets of the COSTIS-system mounted at the BTL of the Cyclone 18/9
Full text linkIntroduction
The COSTIS system is a commercially available target station for the irradiation of solid targets. Up to 3 targets can be provided for irradiation by a slot system. In standard setup the target can be ejected via a pneumatically driven piston system. The target is then allowed to drop down into an open lead container, which can be closed remotely afterwards. The described procedure is well established and reliable. But the concept is limited to low dose targets and environments. The required entering of the cyclotron vault for manual pick up of the container at the cyclotron and the light 18 mm Pb lead shielding of the container itself cause exposure risk for the personnel after long term irradiations with highly activated cyclotron parts and target.
The purpose of this work was the design of an alternative for the pickup and the transport of irradiated targets to minimize the radiation dosage of the personnel during manual handling of the COSTIS-lead container.
Principle
The new designed transport system still uses the software controlled target ejection function of the COSTIS/IBA-system. With ejection the target capsule is allowed to fall into a PTFE-container. To assure a safe target drop into the PTFE container, the gap between the target guiding plate and the PTFE container is smaller than d/2 of the target capsule. After target ejection the PTFE-container can be transferred remotely from target ejection position (1) to the loading station (2) with a target slide. The loading station allows the transfer of the PTFE container remotely into a lead container (60 mm Pb). Now the vault door is used as carrier of the Pb-container. For this purpose a proper fixture for the Pb-container is mounted at the front side of the vault door and via opening the vault door the container is safely transported out of the vault. Outside the container will be finally closed with a lid and transferred to a trolley for further handling. Due to positioning of the container at a certain altitude together with the deep positioning of the target coin inside of the container, the subsequent closing of the container does not cause significant dosage, a more complicated automatic closing system is not mandatory. After replacement of the lead container further transfers can be executed without entering the vault. For this purpose the exchanged Pb-container is placed at the loading station by closing the vault door and a new PTFE-container will be transferred remotely from a magazine onto the target slide, which again can be re-motely positioned at target ejection position. The magazine of PTFE-Containers holds two replacements in accordance with the maximal capacity of the target slot system of the COSTIS station. The remote system of the transport unit uses redundant feedback signals for a reliable and safe operation.
Results and Conclusion
The newly implemented transport system allows a significant reduction of the radiation dose during pickup and transport of the irradiated solid targets. No entering of the vault is needed after irradiation. The system is highly reliable due to its redundant and straightforward design (2-fold position switches and photoelectric barriers). Due to fixed attachment points in the vault and at the BTL the mobile unit can be easily removed or mounted. The system is maintenance free and all parts easy accessible.
For further handling of the targets lead containers were design to fit in the transfer locks of hot cells. The transfer can be carried out directly from the trolley. Container lid and PTFE container are suited for manipulator handling in hot cells
Cyclotron production and cyclometallation chemistry of 192Ir
Full text linkIntroduction
To explore new questions and techniques in nuclear medicine, new isotopes with novel chemical and nuclear properties must be developed. We are interested in the small cyclotron production of new radiometals for the development of new radiopharmaceuticals (RX). In an example of RX multifunctionality, Luminescence Cell Imaging (LCI) has been combined with radio-isotopes to allow compounds that can be imaged with both optical microscopy and nuclear techniques [1]. Within this field, iridium cy-clometalates have good potential with excellent photophysical properties [2]. As well, low specific activity iridium-192 has found use in brachy-therapy as a high-intensity beta emitter [3]. Despite this, iridium radioisotopes have yet to be applied to cyclometalation chemistry, or a radiochemical isolation method developed for carrier free production on a medical cyclotron. Our goal is to demonstrate the feasibility of the production and isolation of radio-iridium, and its application to cyclometalate chemistry as a potentially interesting tool for nuclear medicine research.
Materials and Methods
Following literature precedent [4], natural osmium was electroplated onto a silver disc from basic media containing osmium tetroxide and sulphamic acid. The thin deposits obtained (15–20 mg cm−2) were weighed and characterized with scanning electron microscopy.
Targets were irradiated using the TRIUMF TR13 cyclotron, delivering 12.5 MeV protons to the target disc. Initial bombardments were per-formed at 5 μA; gamma spectra of the targets were collected 24 hours after end of bombardment.
The irradiated material was oxidized, dissolved from the target backing, and separated via anion exchange.
In parallel to the isotope production work, non-radioactive iridium was used to define a chemical procedure suitable for the synthesis of model iridium cyclometalate compounds given low concentrations of radioiridium. These experiments will be performed with radioactive iridium in the next step of the research project.
Results and Conclusion
Proton bombardment of natural osmium yielded a range of iridium isotopes, with characteristic spectral lines corresponding to 186-190Ir, and 192Ir; no other characteristic radiation was observed. The EOB activity of each isotope was then used in thin target calculations to approximate their (p,n) cross section. Preliminary cross section measurements of the 192Os(p,n)192Ir reaction (53 ± 13 mb @ 12.5 MeV) confirm published data (52.3 ± 5.7 mb @ 12.2 MeV) [6], and provide as-yet unpublished data on the lower mass number isotopes.
The progress of radioactive iridium through the radiochemical separation was tracked with a dose calibrator; the osmium complex formed was brightly coloured and could be seen retained on the column. The overall efficiency of the process is estimated at 80 %. Radioactive cyclometallation chemistry is currently under-way.
The production and isolation of a range of iridium isotopes in a chemically useful form was demonstrated, and is ready to be applied to a cyclometalate model compound. Future work will investigate the production of 192Ir from enriched 192Os
In vivo cell tracking with 52Mn PET: Targetry, Separation, and Applications
Full text linkIntroduction
52Mn (t½ =5.59 d, β+ = 29.6%, Eβmax = 0.58 MeV) has great potential as a long lived PET isotope for use in cell tracking studies, observation of immunologic response to disease states, or as an alternative to manganese-based MRI contrast agents. Its favorable max positron energy leads to superb imaging resolution, comparable to that of 18F.[1]
Manganese is naturally taken up by cells via a multitude of pathways including the divalent metal transporter (DMT1), ZIP8, transferrin receptors (TfR), store-operated Ca2+ channels (SOC-Ca2+), and ionotropic glutamate receptor Ca2+ channels (GluR).[2] These natural transport mechanisms make 52Mn an attractive isotope for applications necessitating non-perturbative cell uptake. In particular, cell tracking is critical to the development and translation of stem cell therapies in regenerative medicine. Alternative-ly, 52Mn could be used in immunotherapy techniques such as adoptive cellular therapy (ACT) to evaluate the ability of external immune cells to reach their intended target.
Material and Methods
52Mn was produced by natCr(p,x)52Mn using 16 MeV protons. The average thick target production yield was 0.23 mCi/µA-h with less than 0.25% co-production of 54Mn. Small amounts of 51Cr were observed in the target, but were absent from the radiochemically separated product.
Target construction consisted of a water jet cooled chromium disc (3/4” diameter, 0.4” thick). Targets were purchased from Kamis Inc, and are 99.95% pure. Targets withstood beam currents of 30 µA with no visible aberration.
Chromium targets were etched by concentrated HCl following bombardment. Mn2+ ions were extracted from 9M HCl to 0.8M trioctylamine in cyclohexane leaving the bulk chromium in the aqueous phase. After isolating the organic phase, 0.001M NH4OH was used to back-extract the Mn2+ ions to aqueous phase. This purification cycle was conducted a total of three times for each 52Mn production.
Results and Conclusion
For a starting bulk chromium mass of 456 ± 1 mg, a post-separation chromium mass of 5.35 ± 0.04 ng was measured by microwave plasma atomic emission spectrometry (MP-AES). This mass reduction corresponds to an average separation factor of 440 for a single purification cycle. Each purification cycle had a 52Mn recovery efficiency of 73 ± 7 % (n = 6), resulting in an overall separation efficiency of approximately 35 %. These efficiencies and separation factors agree reasonably well with the work conducted by Lahiri et. al.[3] Prior to use, the product was passed through a C-18 Sep-Pak to remove any residual organic phase.
After four target irradiations and etchings, some pitting became noticeable on the target face. These have not yet compromised the o-ring seal with the target deplater, but it is possible that target replacement after every 6–9 52Mn productions will be necessary moving forward.
Following the successful separation of 52Mn from chromium, in vitro experiments were conducted to demonstrate the uptake of 52Mn by human stem cells and mouse tumor cells. A linear uptake response was observed as a function of the amount of activity exposed to the cells for both cell models. These experiments have shown great promise for 52Mn as a long-lived PET isotope in cell tracking studies. Details will be presented