Introduction Access to radiometals suitable for labeling novel molecular imaging agents requires that they be routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for a radiometal of interest is necessary, both of which can be significant hurdles in availability of less common isotopes. Herein, we describe the production of 44Sc, 68Ga, 89Zr, 86Y and 94mTc in a solution target which allows for the production of various radiometallic isotopes, enabling rapid isotope-biomolecule pairing optimization for tracer development. Work on solution targets has also been performed by other groups [e.g. 1, 2]. Material and Methods Solutions containing a high concentration of natural-abundance zinc nitrate, yttrium nitrate, calcium nitrate [3], strontium nitrate or ammonium heptamolybdate [4] were irradiated on a 13 MeV cyclotron using a standard liquid target. Some of the solutions contained additional hydrogen peroxide or nitric acid to improve solubility and reduce pressure rise in the target during irradiation. Yields calculated using theoretical cross sections (EMPIRE [5]) were compared to the measured yields. In addition, we tested a thermo-syphon target design for the production of 44Sc. Chemical separation of the product from the target material was carried out on a remote apparatus modeled after that of Siikanen [6]. Results and Conclusion The proposed approach enabled the production of quantities sufficient for chemical or biological studies for all metals discussed. In the case of 68Ga, activity up to 480 ± 22 MBq was obtained from a one hour run with a beam current of 7 µA, potentially enabling larger scale clinical production. Considering all reactions, the ratio of theoretical saturation yields to experimental yields ranges from 0.8 for 94mTc to 4.4 for 44Sc. The thermo-syphon target exhibited an increase of current on the target by a factor of 2.5 and an increase in yield by a factor of five for the production of 44Sc. Separation methods were developed for all isotopes and separation efficiency ranges from 71 ± 1 % for 94mTc to 99 ± 4 % for 86Y. 44Sc, 68Ga, and 86Y were successfully used in labeling studies with a model 1,4,7,10-tetrazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelate, while 89Zr coordination behavior was tested using desferrioxamine-alkyne (DFO-alkyne). In summary, we present a promising new method to produce a suite of radiometals in a liquid target. Future work will continue to expand the list of radiometals and to apply this approach to the development of various peptide, protein and antibody radiotracers.

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.

Introduction Access to radiometals suitable for labeling novel molecular imaging agents requires that they be routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for a radiometal of interest is necessary, both of which can be significant hurdles in availability of less common isotopes. Herein, we describe the production of 44Sc, 68Ga, 89Zr, 86Y and 94mTc in a solution target which allows for the production of various radiometallic isotopes, enabling rapid isotope-biomolecule pairing optimization for tracer development. Work on solution targets has also been performed by other groups [e.g. 1, 2]. Material and Methods Solutions containing a high concentration of natural-abundance zinc nitrate, yttrium nitrate, calcium nitrate [3], strontium nitrate or ammonium heptamolybdate [4] were irradiated on a 13 MeV cyclotron using a standard liquid target. Some of the solutions contained additional hydrogen peroxide or nitric acid to improve solubility and reduce pressure rise in the target during irradiation. Yields calculated using theoretical cross sections (EMPIRE [5]) were compared to the measured yields. In addition, we tested a thermo-syphon target design for the production of 44Sc. Chemical separation of the product from the target material was carried out on a remote apparatus modeled after that of Siikanen [6]. Results and Conclusion The proposed approach enabled the production of quantities sufficient for chemical or biological studies for all metals discussed. In the case of 68Ga, activity up to 480 ± 22 MBq was obtained from a one hour run with a beam current of 7 µA, potentially enabling larger scale clinical production. Considering all reactions, the ratio of theoretical saturation yields to experimental yields ranges from 0.8 for 94mTc to 4.4 for 44Sc. The thermo-syphon target exhibited an increase of current on the target by a factor of 2.5 and an increase in yield by a factor of five for the production of 44Sc. Separation methods were developed for all isotopes and separation efficiency ranges from 71 ± 1 % for 94mTc to 99 ± 4 % for 86Y. 44Sc, 68Ga, and 86Y were successfully used in labeling studies with a model 1,4,7,10-tetrazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelate, while 89Zr coordination behavior was tested using desferrioxamine-alkyne (DFO-alkyne). In summary, we present a promising new method to produce a suite of radiometals in a liquid target. Future work will continue to expand the list of radiometals and to apply this approach to the development of various peptide, protein and antibody radiotracers.

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.