Development of radiometal automated laboratory workbench

Introduction 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

Zoledronic Acid Preserves Bone Structure and Increases Survival but Does Not Limit Tumour Incidence in a Prostate Cancer Bone Metastasis Model

Background The bisphosphonate, zoledronic acid (ZOL), can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM), to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. Methods The model involves intracardiac injection for arterial dissemination of the RM1(BM) cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b) and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. Findings Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM) cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. Conclusions ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a requirement for establishment of these bone tumours

Development of radiometal automated laboratory workbench

Introduction 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

Legislative Documents

Also, variously referred to as: House bills; House documents; House legislative documents; legislative documents; General Court documents

Development of radiometal automated laboratory workbench

Introduction 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 gas target system for 83Rb production

Introduction Short-lived isomer 83mKr (T½ = 1.83 h) is an ideal calibration source in several low-energy experiments like or KATRIN (determining the neutrino rest mass, monitoring high voltage stability and investigation of the main spectrometer properties) or XENON (detection of the dark matter). The isomer 83mKr is formed by decay of 83Rb (T½ = 86.2 d) that can be produced predominantly via the reaction 84Kr(p,2n)83Rb by irradiation of natKr (57 % abundance of 84Kr). The design and construction of the new gas target for effective production of radionuclide 83Rb as well as target processing will be shortly described. Material and Methods For the target design, we selected the following criteria: minimizing activation of target components; efficient cooling system allowing higher beam currents; easy handling; high life-time of the target chamber (low impact of the irradiation and radionuclide separation process on the target chamber surface and 83Rb recovery). The target consists of three parts: 1. Water cooled aluminium (alloy EN 6082) mechanical interface for easy connection of the target to the beam line. It also serves as a beam collimator (diameter 9 mm). 2. Holder of He-cooled foils (vacuum separation foil – Havar 0.025 mm, target body window – Ti 0.1 mm). 3. Aluminium (alloy EN 6082) water cooled target body with 150mm long cone-shaped target chamber of the volume 27.1 ml. Internal surface of the chamber is nickel-coated. The target filled with natural Kr of purity 0.9999 and absolute pressure 13 bar was irradiated on the external beam of the isochronous cyclotron U-120M of the NPI AS CR. The proton beam energy was set so that it is decreased after deg-radation in the separation foils to 25.6 MeV. Beam energy loss in the natural Kr gas filling is 9.6 MeV. The target was tested up to 25 µA beam current. After irradiation, the target is left for a week to let the short-lived activation products to decay. Then, 83Rb is washed out from the target walls by two portions of freshly prepared de-ionized water, target is rinsed by high-purity ethanol and dried. The two portions of 83Rb aqueous solution are then connected and activity and radionuclidic purity of the product is determined via γ-spectrometry (HPGe detector). Large-distance sample-detector measurements of the target prior and after the separation are used in order to determine recovery of 83Rb. Results and Conclusion The new gas target for routine production of 83Rb was successfully designed, tested and im-plemented for regular 83Rb production. Six-hour irradiation with 15 µA proton beam resulted repeatedly in ca 300 MBq of 83Rb (EOB). Besides 83Rb, we identified in the separated product also 84Rb (T½ = 32.82 d) at levels ca 31 % of the 83Rb activity (EOB) and 86Rb (T½ = 18.631 d) at levels ca 8 % of the 83Rb activity (EOB). Both radionuclidic impurities do not disturb the use of 83Rb, since none of them emanates any radioactive krypton isotope. Moreover, their relative content decreases in time. Rubidium isotopes are recovered from the target almost quantitatively (98–99 %)