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.

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 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.

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.