Introduction The effective specific activity of a radioisotope is an indirect and highly useful way to describe a radioactive sample’s purity. A high effective specific activity combines the concept of an isotopically pure product with suitability via selectivity of a particular chelating body. The primary goals of this work are twofold: 1) To determine which metallic impurities have the largest impact on the effective specific activity for a given chelator, and 2) to form a model based on the binding affinities of each metal for to calculate a ‘theoretical effective specific activ-ity’ from broad band trace metal analysis. If successful, this information can be used to guide the production of high specific activity products through the systematic elimination of high-impact metallic impurities. Material and Methods Phosphor plate thin layer chromatography (TLC) was used to measure the effective specific activ-ity of 64Cu by NOTA and DOTA, and 89Zr by des-feral (DF). Typical measured effective specific activities are 2–5 Ci/μmol for 64Cu and 1–2 Ci/μmol for 89Zr. Samples were created containing increasing cod competitive burdens (X) of CuCl2, ZnCl2, FeCl2, NiCl2, CrCl3, CoCl2, MnCl2, and YCl3. Standard concentrations were measured by microwave plasma atomic emission spectrometry. 50 pmol of NOTA, DOTA, or DF were added following the activity aliquots of 64Cu or 89Zr. Labeling efficien-cies (64Cu-NOTA, 64Cu-DOTA, 89Zr-DF) were measured using TLC’s, and were fit by linear regression to the form f(X) = b/(1 − AX), where A is the chelation affinity (inverse of dissociation constant) and X is the molar ratio of the metallic impurity to the amount of chelator. Results and Conclusion Affinity of Zr for DF was assumed to be unity, while the affinities of Cu for NOTA and DOTA were explicitly measured and were found to be 0.93 ± 0.13 and 5.2 ± 3.2 respectively. It was found that Cu had the highest affinity for NOTA by a factor of 266, and that Zr had the highest affinity for DF by a factor of 40. • In order of decreasing affinity to NOTA: Cu, Zn, Fe, Co, Cr, Y, and Ni • In order of decreasing affinity to DOTA: Cu, Y, Zn, Co, Ni, Cr, and Fe • In order of decreasing affinity to DF: Zr, Y, Cu, Zn, Ni, Fe, Co, Cr These results suggest that aside from the carrier element it is most important to remove zinc from 64Cu products prior to chelation with NOTA and yttrium from 64Cu and 89Zr products prior to chelation with DOTA and DF, respectively. Therefore, it is logical to believe that 89Zr effective specific activities could be greatly improved by secondary separations with the goal of re-moving additional yttrium target material. Chelation affinities of NOTA, DOTA, and DF for several common metals have successfully been investigated. These values will guide our future attempts to provide high effective specific activity 64¬Cu and 89Zr. Furthermore, a preliminary model has been formed to calculate effective specific activity from the quantitative broad band analysis of trace metals. Future work will include chelator affinity measurements for other likely contaminants, such as scandium, titanium, zirconium, molybdenum, niobium, gold, gallium, and germanium. Details will be presented.

Introduction Zr-89 is a useful radionuclide for radiolabeling proteins and other molecules.1,2 There are many reports of cyclotron production of 89Zr by the 89Y (p,n) reaction. Most irradiations use thin metal backed deposits of Y and irradiation currents up to 100 µA or thicker amounts of Y or Y2O3 with ~ 20 µA irradiations.3,4 We are working to develop high specific activity 89Zr using a low energy 11 MeV cyclotron. We have found that target Y metal contains carrier Zr and higher specific activities are achieved with less Y. The goal of this work was to optimize yield while minimizing the amount of Y that was irradiated. Material and Methods All irradiations were done using a Siemens Eclipse 11 MeV proton cyclotron. Y foils were used for the experiments described here. Y2O3 was tried and abandoned due to lower yield and poor heat transfer. Yttrium metal foils from Alfa Aesar, ESPI Metals and Sigma Aldrich, 0.1 to 1 mm in thickness, were tested. Each foil was irradiated for 10 to 15 minutes. The targets to hold the Y foils were made of aluminum and were designed to fit within the “paper burn” unit of the Siemen’s Eclipse target station, allowing the Y target body to be easily inserted and removed from the system. Several Al targets of 2 cm diam. and 7.6 cm long were tested with the face of the targets from 11, 26 or 90o relative to the beam to vary watts cm−2 on the foil. The front of the foils was cooled by He convection and the foil backs by conduction to the Al target body. The target body was cooled by conduction to the water cooled Al sleeve of the target holder. Results and Conclusion The best target was two stacked, 0.25 mm thick, foils to stop beam. 92% of the 89Zr activity was in the front 0.25 mm Y foil. With the greatest slant we could irradiate up to 30 µA of beam on tar-get. However, the 13×30 mm dimensions of the foil was more mass (0.41 g) and lower specific activity than was desired. Redesign of the target gave a target 90o to the beam with 12×12 mm foils (0.15 g/foil) that were undamaged with up to 30 µA irradiation when two foils were used. This design has a reduction in beam at the edges of ~10%. With this design, a single Y foil, 0.25 mm thick sustained over 31 µA of beam and a peak power on target of 270 watts cm−2. The product was radionuclidically pure 89Zr after all 89mZr and small amounts of 13N produced from oxygen at the surface had decayed (TABLE 1). Our conclusion is that the optimum target is a single 0.25 mm thick Y foil to obtain the greatest specific activity at this proton energy. This produces 167 MBq of 89Zr at EOB with a 15 minute and 31 µA irradiation. We are continuing to redesign the clamp design to reduce losses at the edge of the beam.

Introduction The effective specific activity of a radioisotope is an indirect and highly useful way to describe a radioactive sample’s purity. A high effective specific activity combines the concept of an isotopically pure product with suitability via selectivity of a particular chelating body. The primary goals of this work are twofold: 1) To determine which metallic impurities have the largest impact on the effective specific activity for a given chelator, and 2) to form a model based on the binding affinities of each metal for to calculate a ‘theoretical effective specific activ-ity’ from broad band trace metal analysis. If successful, this information can be used to guide the production of high specific activity products through the systematic elimination of high-impact metallic impurities. Material and Methods Phosphor plate thin layer chromatography (TLC) was used to measure the effective specific activ-ity of 64Cu by NOTA and DOTA, and 89Zr by des-feral (DF). Typical measured effective specific activities are 2–5 Ci/μmol for 64Cu and 1–2 Ci/μmol for 89Zr. Samples were created containing increasing cod competitive burdens (X) of CuCl2, ZnCl2, FeCl2, NiCl2, CrCl3, CoCl2, MnCl2, and YCl3. Standard concentrations were measured by microwave plasma atomic emission spectrometry. 50 pmol of NOTA, DOTA, or DF were added following the activity aliquots of 64Cu or 89Zr. Labeling efficien-cies (64Cu-NOTA, 64Cu-DOTA, 89Zr-DF) were measured using TLC’s, and were fit by linear regression to the form f(X) = b/(1 − AX), where A is the chelation affinity (inverse of dissociation constant) and X is the molar ratio of the metallic impurity to the amount of chelator. Results and Conclusion Affinity of Zr for DF was assumed to be unity, while the affinities of Cu for NOTA and DOTA were explicitly measured and were found to be 0.93 ± 0.13 and 5.2 ± 3.2 respectively. It was found that Cu had the highest affinity for NOTA by a factor of 266, and that Zr had the highest affinity for DF by a factor of 40. • In order of decreasing affinity to NOTA: Cu, Zn, Fe, Co, Cr, Y, and Ni • In order of decreasing affinity to DOTA: Cu, Y, Zn, Co, Ni, Cr, and Fe • In order of decreasing affinity to DF: Zr, Y, Cu, Zn, Ni, Fe, Co, Cr These results suggest that aside from the carrier element it is most important to remove zinc from 64Cu products prior to chelation with NOTA and yttrium from 64Cu and 89Zr products prior to chelation with DOTA and DF, respectively. Therefore, it is logical to believe that 89Zr effective specific activities could be greatly improved by secondary separations with the goal of re-moving additional yttrium target material. Chelation affinities of NOTA, DOTA, and DF for several common metals have successfully been investigated. These values will guide our future attempts to provide high effective specific activity 64¬Cu and 89Zr. Furthermore, a preliminary model has been formed to calculate effective specific activity from the quantitative broad band analysis of trace metals. Future work will include chelator affinity measurements for other likely contaminants, such as scandium, titanium, zirconium, molybdenum, niobium, gold, gallium, and germanium. Details will be presented.

Introduction Zr-89 is a useful radionuclide for radiolabeling proteins and other molecules.1,2 There are many reports of cyclotron production of 89Zr by the 89Y (p,n) reaction. Most irradiations use thin metal backed deposits of Y and irradiation currents up to 100 µA or thicker amounts of Y or Y2O3 with ~ 20 µA irradiations.3,4 We are working to develop high specific activity 89Zr using a low energy 11 MeV cyclotron. We have found that target Y metal contains carrier Zr and higher specific activities are achieved with less Y. The goal of this work was to optimize yield while minimizing the amount of Y that was irradiated. Material and Methods All irradiations were done using a Siemens Eclipse 11 MeV proton cyclotron. Y foils were used for the experiments described here. Y2O3 was tried and abandoned due to lower yield and poor heat transfer. Yttrium metal foils from Alfa Aesar, ESPI Metals and Sigma Aldrich, 0.1 to 1 mm in thickness, were tested. Each foil was irradiated for 10 to 15 minutes. The targets to hold the Y foils were made of aluminum and were designed to fit within the “paper burn” unit of the Siemen’s Eclipse target station, allowing the Y target body to be easily inserted and removed from the system. Several Al targets of 2 cm diam. and 7.6 cm long were tested with the face of the targets from 11, 26 or 90o relative to the beam to vary watts cm−2 on the foil. The front of the foils was cooled by He convection and the foil backs by conduction to the Al target body. The target body was cooled by conduction to the water cooled Al sleeve of the target holder. Results and Conclusion The best target was two stacked, 0.25 mm thick, foils to stop beam. 92% of the 89Zr activity was in the front 0.25 mm Y foil. With the greatest slant we could irradiate up to 30 µA of beam on tar-get. However, the 13×30 mm dimensions of the foil was more mass (0.41 g) and lower specific activity than was desired. Redesign of the target gave a target 90o to the beam with 12×12 mm foils (0.15 g/foil) that were undamaged with up to 30 µA irradiation when two foils were used. This design has a reduction in beam at the edges of ~10%. With this design, a single Y foil, 0.25 mm thick sustained over 31 µA of beam and a peak power on target of 270 watts cm−2. The product was radionuclidically pure 89Zr after all 89mZr and small amounts of 13N produced from oxygen at the surface had decayed (TABLE 1). Our conclusion is that the optimum target is a single 0.25 mm thick Y foil to obtain the greatest specific activity at this proton energy. This produces 167 MBq of 89Zr at EOB with a 15 minute and 31 µA irradiation. We are continuing to redesign the clamp design to reduce losses at the edge of the beam.