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Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (68Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for 68Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting 68Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [68Ga]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high 68Ga recovery and apparent molar activity. In the future, 68Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of 68Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns. [ABSTRACT FROM AUTHOR]

Natural-abundance phosphomolybdic acid (H 3 (Mo 12 PO 40) ‧12H 2 O, 0.181–0.552 g Mo/mL) solutions were irradiated with 12.9 MeV protons on a GE PETtrace cyclotron using an adapted standard liquid target. Technetium-94m (94mTc) was produced through the 94Mo(p,n)94mTc nuclear reaction with saturation yields of up to 53 ± 6 MBq/μA. End of bombardment activities of 161 ± 17 MBq and 157 ± 7 MBq were achieved for the 0.552 g Mo/mL solution (10 μA for 30 min) and 0.181 g Mo/mL solution (15 μA for 60 min), respectively. No visible degradation of the niobium target body and foil were seen during the irradiations of up to 15 μA for 60 min. The produced 94mTc was separated from the target phosphomolybdic acid solution with >98% recovery using an aqueous biphasic extraction resin. Compared to previous reported liquid target methods for 94mTc production, the better production yield, in-target solution stability during irradiation and 94mTc separation recovery of phosphomolybdic acid makes it a very promising target material for routine clinical 94mTc production at medical facilities with liquid targets already installed for 18F production. • 94mTc could bring the benefits of Tc-tracer research to the field of total body PET. • Optimised production of 94mTc in cyclotron liquid target. • Proton-irradiation of phosphomolybdic acid with saturation yields up to 53 MBq/μA. • Excellent Tc/Mo separation using aqueous biphasic extraction resin. [ABSTRACT FROM AUTHOR]

Abstract Purpose To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2–0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use. Results The decay corrected yield of 68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia ( 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). Conclusion Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators.

Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 (68Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for 68Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting 68Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [68Ga]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high 68Ga recovery and apparent molar activity. In the future, 68Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of 68Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns.

Due to increased demand, cyclotron has an expanding role in producing Gallium-68 (68Ga) radiopharmaceuticals using solid and liquid targets. Though the liquid target produces lower end-of-bombardment activity compared to the solid target, our study presents the performance of 68Ga radiopharmaceuticals production using the liquid target by evaluating the end-of-bombardment activity and the end-of-purification activity of [68Ga]GaCl 3. We also present the effect of increasing irradiation time, which significantly improves the end-of-synthesis yield. From the result obtained, the end-of-bombardment activity produced was 4.48 GBq, and the [68Ga]GaCl 3 end-of-purification activity produced was 2.51 GBq with below-limit metallic impurities. Increasing the irradiation time showed a significant increase in the end-of-synthesis activity from 1.33 GBq to 1.95 GBq for [68Ga]Ga-PSMA-11 and from 1.13 GBq to 1.74 GBq for [68Ga]Ga-DOTA-TATE. Based on the improvements made, the liquid target production of 68Ga radiopharmaceuticals is feasible and reproducible to accommodate up to 5 patients per production. In addition, this work also discusses the issues encountered, together with the possible corrective and preventative measures. [Display omitted] • More than 1.7 GBq [68Ga]Ga-PSMA and [68Ga]Ga-DOTATATE is produced using liquid target. • Increasing the target solution's HNO 3 concentration and the irradiation time improves the End of Synthesis (EOS) yield. • Consistent production of 68Ga-radiopharmaceuticals can be achieved through proper maintenance and preventative measures. [ABSTRACT FROM AUTHOR]

Abstract Background We recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target. Results Following installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic. Conclusions The combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use.

To optimize 68Ga production using a liquid cyclotron target, investigations were performed to compare production yields using different concentrations of [68Zn]Zn(NO 3) 2 , nitric acid, and irradiation parameters. Different concentrations of [68Zn]Zn(NO 3) 2 (0.6 M, 1.2 M and 1.42 M) in varying normality of nitric acid (0.8–1.5 N) were prepared and irradiated with protons (incident energy ~14 MeV) using a BMLT-2 liquid target at different beam currents (30–50 μA) and irradiation times (30–60 min). The 68Ga production and saturation yields were calculated and compared. [68Ga]GaCl 3 was isolated using in-house developed hydroxamate resin and optimized for routine application. Recycling of [68Zn]Zn(NO 3) 2 from the recovered target solution was also investigated. On increasing concentration of [68Zn]Zn(NO 3) 2 from 0.6 M to 1.2 M in 0.8 N nitric acid, decay corrected yield of 68Ga at EOB was found to be 1.64 GBq (44.4 mCi) and 3.37 GBq (91.0 mCi), respectively at 30 μA beam current, indicating production yield was proportional to zinc nitrate concentration for a 30 min irradiation. However, when beam current was increased to 40 μA while maintaining nitric acid concentration at 0.8 N, the proportional relationship of 68Zn-concentration with 68Ga production yield was lost [0.6 M, 2.29 GBq (61.9 mCi); 1.2 M, 3.6 GBq (97.3 mCi)] for a 30 min irradiation. In fact, the effect was more profound for 60 min irradiations [0.6 M, 2.96 GBq (80.0 mCi); 1.2 M, 4.25 GBq (115 mCi)]. Increasing nitric acid concentration to 1.25–1.5 N improved 68Ga production yield for 40 μA, 60-min irradiations (1.2 M; 5.17 GBq (140 mCi)). MP-AES analysis showed metal impurities as <0.20 μg Ga (n = 3), <0.93 μg Zn (n = 3) and < 2.7 μg Fe (n = 3). Based on above finding, 1.42 M [68Zn]Zn(NO 3) 2 in 1.2 N-HNO 3 solutions were also studied to achieve highest production yields of 9.85 ± 2.09 GBq (266 ± 57 mCi) for 60 min irradiation at 40 μA beam current. After recycling,> 99% pure recycled [68Zn]zinc nitrate was obtained in 82.6 ± 13.6% yield. 68Ga production yields were dependent on all four variables: concentrations of [68Zn]Zn(NO 3) 2 and nitric acid, beam current and duration of irradiation. Of note, increasing beam current and irradiation time may require increased concentrations of nitric acid to achieve expected increments in 68Ga production yield. [ABSTRACT FROM AUTHOR]

Objective The objectives of the present work were to improve the cyclotron production yield of 89 Zr using a solution target, develop a practical synthesis of the hydroxamate resin used to process the target, and develop a biocompatible medium for 89 Zr elution from the hydroxamate resin. Methods A new solution target (BMLT-2) with enhanced heat dissipation capabilities was designed by using helium-cooled dual foils (0.2 mm Al and 25 μ Havar) and an enhanced water-cooled, elongated solution cavity in the target insert. Irradiations were performed with 14 MeV protons on a 2 M solution of yttrium nitrate in 1.25 M nitric acid at 40-μA beam current for 2 h in a closed system. Zirconium-89 was separated from Y by use of a hydroxamate resin. A one-pot synthesis of hydroxamate resin was accomplished by activating the carboxylate groups on a carboxymethyl cation exchange resin using methyl chloroformate followed by reaction with hydroxylamine hydrochloride. After trapping of 89 Zr on hydroxamate resin and rinsing the resin with HCl and water to release Y, 89 Zr was eluted with 1.2 M K 2 HPO 4 /KH 2 PO 4 buffer (pH 3.5). ICP-MS was used to measure metal contaminants in the final 89 Zr solution. Results The BMLT-2 target produced 349 ± 49 MBq (9.4 ± 1.2 mCi) of 89 Zr at the end of irradiation with a specific activity of 1.18 ± 0.79 GBq/μg. The hydroxamate resin prepared using the new synthesis method showed a trapping efficiency of 93% with a 75 mg resin bed and 96–97% with a 100–120 mg resin bed. The elution efficiency of 89 Zr with 1.2 M K 2 HPO 4 /KH 2 PO 4 solution was found to be 91.7 ± 3.7%, compared to > 95% for 1 M oxalic acid. Elution with phosphate buffer gave very small levels of metal contaminants: Al = 0.40–0.86 μg (n = 2), Fe = 1.22 ± 0.71 μg (n = 3), Y = 0.29 μg (n = 1). Conclusions The BMLT-2 target allowed doubling of the beam current for production of 89 Zr, resulting in a greater than 2-fold increase in production yield in comparison with a conventional liquid target. The new one-pot synthesis of hydroxamate resin provides a simpler synthesis method for the 89 Zr trapping resin. Finally, phosphate buffer elutes the 89 Zrfrom the hydroxamate resin in high efficiency while at the same time providing a more biocompatible medium for subsequent use of 89 Zr. [ABSTRACT FROM AUTHOR]

A high power [F-18] fluoride target package for the RDS-112 cyclotron has been designed, tested, and commercially deployed. The upgrade includes the CF-1000 target, a 1.3 kW water target with an established commercial history on RDS-111/Eclipse cyclotrons, and a redesigned collimator with improved heat rejection capabilities. Conjugate heat transfer analyses were employed to both evaluate the existing collimator capabilities and design a suitable high current replacement. [ABSTRACT FROM AUTHOR]

Designing and implementing various radionuclide production methods guarantees a sustainable supply, which is important for medical use. The use of medical cyclotrons for radiometal production can increase the availability of gallium-68 ( 68 Ga) radiopharmaceuticals. Although generators have greatly influenced the demand for 68 Ga radiopharmaceuticals, the use of medical cyclotrons is currently being explored. The resulting 68 Ga production is several times higher than obtained from a generator. Moreover, the use of solid targets yields end of purification and end of synthesis (EOS) of up to 194 GBq and 72 GBq, respectively. Furthermore, experiments employing liquid targets have provided promising results, with an EOS of 3 GBq for [ 68 Ga]Ga-PSMA-11. However, some processes can be further optimized, specifically purification, to achieve high 68 Ga recovery and apparent molar activity. In the future, 68 Ga will probably remain one of the most in-demand radionuclides; however, careful consideration is needed regarding how to reduce the production costs. Thus, this review aimed to discuss the production of 68 Ga radiopharmaceuticals using Advanced Cyclotron Systems, Inc. (ACSI, Richmond, BC, Canada) Richmond, Canada and GE Healthcare, Wisconsin, USA cyclotrons, its related factors, and regulatory concerns.

Abstract: Objective: The existing solid target production method of radiometals requires high capital and operational expenditures, which limit the production of radiometals to the small fraction of cyclotron facilities that are equipped with solid target systems. Our objective is to develop a robust solution target method, which can be applicable to a wide array of radiometals and would be simply and easily adopted by existing cyclotron facility for the routine production of radiometals. Method: We have developed a simplified, solution target approach for production of 89Zr using a niobium target by 14 MeV energy proton bombardment of aqueous solutions of yttrium salts via the 89Y(p,n)89Zr nuclear reaction. The production conditions were optimized, following a detailed mechanistic study of the gas evolution. Results: Although the solution target approach avoided the expense and complication of solid target processing, rapid radiolytic formation of gases in the target represents a major impediment in the success of solution target. To address this challenge we performed a systematic mechanistic study of gas evolution. Gas evolution was found to be predominantly due to decomposition of water to molecular hydrogen and oxygen. The rate of gas evolutions varied >40-fold depending on solution composition even under the same irradiation condition. With chloride salts, the rate of gas evolution increased in the order rank Na

Abstract: Zirconium-89 is an attractive metallo-radionuclide for use in immuno-PET due to favorable decay characteristics. Standardized methods for the routine production and isolation of high-purity and high-specific-activity 89Zr using a small cyclotron are reported. Optimized cyclotron conditions reveal high average yields of 1.52±0.11 mCi/μA·h at a proton beam energy of 15 MeV and current of 15 μA using a solid, commercially available 89Y-foil target (0.1 mm, 100% natural abundance). 89Zr was isolated in high radionuclidic and radiochemical purity (>99.99%) as [89Zr]Zr-oxalate by using a solid-phase hydroxamate resin with >99.5% recovery of the radioactivity. The effective specific-activity of 89Zr was found to be in the range 5.28–13.43 mCi/μg (470–1195 Ci/mmol) of zirconium. New methods for the facile production of [89Zr]Zr-chloride are reported. Radiolabeling studies using the trihydroxamate ligand desferrioxamine B (DFO) gave 100% radiochemical yields in <15 min at room temperature, and in vitro stability measurements confirmed that [89Zr]Zr-DFO is stable with respect to ligand dissociation in human serum for >7 days. Small-animal positron emission tomography (PET) imaging studies have demonstrated that free 89Zr(IV) ions administered as [89Zr]Zr-chloride accumulate in the liver, whilst [89Zr]Zr-DFO is excreted rapidly via the kidneys within <20 min. These results have important implication for the analysis of immuno-PET imaging of 89Zr-labeled monoclonal antibodies. The detailed methods described can be easily translated to other radiochemistry facilities and will facilitate the use of 89Zr in both basic science and clinical investigations. [Copyright &y& Elsevier]

Due to the advent of various biologics like antibodies, proteins, cells, viruses, and extracellular vesicles as biomarkers for disease diagnosis, progression, and as therapeutics, there exists a need to have a simple and ready to use radiolabeling synthon to enable noninvasive imaging trafficking studies. Previously, we reported [ 89 Zr]zirconium- p -isothiocyanatobenzyl-desferrioxamine ([ 89 Zr]Zr-DBN) as a synthon for the radiolabeling of biologics to allow PET imaging of cell trafficking. In this study, we focused on improving the molar activity (A m ) of [ 89 Zr]Zr-DBN, by enhancing 89 Zr production on a low-energy cyclotron and developing a new reverse phase HPLC method to purify [ 89 Zr]Zr-DBN. To enhance 89 Zr production, a new solid target was designed, and production yield was optimized by varying, thickness of yttrium foil, beam current, irradiation duration and proton beam energy. After optimization, 4.78±0.33 GBq (129.3±8.9 mCi) of 89 Zr was produced at 40 µA for 180 min (3 h) proton irradiation decay corrected to the end of bombardment with a saturation yield of 4.56±0.31 MBq/µA. Additionally, after reverse phase HPLC purification the molar activity of [ 89 Zr]Zr-DBN was found to be in 165-316 GBq/µmol range. The high molar activity of [ 89 Zr]Zr-DBN also allowed radiolabeling of low concentration of proteins in relatively higher yield. The stability of [ 89 Zr]Zr-DBN was measured over time with and without the presence of ascorbic acid. The newly designed solid target assembly and HPLC method of [ 89 Zr]Zr-DBN purification can be adopted in the routine production of 89 Zr and [ 89 Zr]Zr-DBN, respectively., Competing Interests: None., (AJNMMI Copyright © 2022.)

Purpose: To optimize the direct production of 68Ga on a cyclotron, via the 68Zn(p,n)68Ga reaction using a liquid cyclotron target. We Investigated the yield of cyclotron-produced 68Ga, extraction of [68Ga]GaCl3 and subsequent [68Ga]Ga-PSMA-11 labeling using an automated synthesis module. Methods: Irradiations of a 1.0 M solution of [68Zn]Zn(NO3)2 in dilute (0.2–0.3 M) HNO3 were conducted using GE PETtrace cyclotrons and GE 68Ga liquid targets. The proton beam energy was degraded to a nominal 14.3 MeV to minimize the co-production of 67Ga through the 68Zn(p,2n)67Ga reaction without unduly compromising 68Ga yields. We also evaluated the effects of varying beam times (50–75 min) and beam currents (27–40 μA). Crude 68Ga production was measured. The extraction of [68Ga]GaCl3 was performed using a 2 column solid phase method on the GE FASTlab Developer platform. Extracted [68Ga]GaCl3 was used to label [68Ga]Ga-PSMA-11 that was intended for clinical use. Results: The decay corrected yield of 68Ga at EOB was typically > 3.7 GBq (100 mCi) for a 60 min beam, with irradiations of [68Zn]Zn(NO3)2 at 0.3 M HNO3. Target/chemistry performance was more consistent when compared with 0.2 M HNO3. Radionuclidic purity of 68Ga was typically > 99.8% at EOB and met the requirements specified in the European Pharmacopoeia (< 2% combined 66/67Ga) for a practical clinical product shelf-life. The activity yield of [68Ga]GaCl3 was typically > 50% (~ 1.85 GBq, 50 mCi); yields improved as processes were optimized. Labeling yields for [68Ga]Ga-PSMA-11 were near quantitative (~ 1.67 GBq, 45 mCi) at EOS. Cyclotron produced [68Ga]Ga-PSMA-11 underwent full quality control, stability and sterility testing, and was implemented for human use at the University of Michigan as an Investigational New Drug through the US FDA and also at the Royal Prince Alfred Hospital (RPA). Conclusion: Direct cyclotron irradiation of a liquid target provides clinically relevant quantities of [68Ga]Ga-PSMA-11 and is a viable alternative to traditional 68Ge/68Ga generators. [ABSTRACT FROM AUTHOR]

Background: We recently upgraded our [18F]fludeoxyglucose (FDG) production capabilities with the goal of futureproofing our FDG clinical supply, expanding the number of batches of FDG we can manufacture each day, and improving patient throughput in our nuclear medicine clinic. In this paper we report upgrade of the synthesis modules to the GE FASTLab 2 platform (Phase 1) and cyclotron updates (Phase 2) from both practical and regulatory perspectives. We summarize our experience manufacturing FDG on the FASTLab 2 module with a high-yielding self-shielded niobium (Nb) fluorine-18 target.Results: Following installation of Nb targets for production of fluorine-18, a 55 μA beam for 22 min generated 1330 ± 153 mCi of [18F]fluoride. Using these cyclotron beam parameters in combination with the FASTLab 2, activity yields (AY) of FDG were 957 ± 102 mCi at EOS, corresponding to 72% non-corrected AY (n = 235). Our workflow, inventory management and regulatory compliance have been greatly simplified following the synthesis module and cyclotron upgrades, and patient wait times for FDG PET have been cut in half at our nuclear medicine clinic.Conclusions: The combination of FASTlab 2 and self-shielded Nb fluorine-18 targets have improved our yield of FDG, and enabled reliable and repeatable manufacture of the radiotracer for clinical use. [ABSTRACT FROM AUTHOR]

The objective of the present work is to extend the applicability of the solution target approach to the production of (68)Ga using a low energy cyclotron. Since the developed method does not require solid target infrastructure, it offers a convenient alternative to (68)Ge/(68)Ga generators for the routine production of (68)Ga. A new solution target with enhanced heat exchange capacity was designed and utilized with dual foils of Al (0.20 mm) and Havar (0.038 mm) separated by helium cooling to degrade the proton energy to ~14 MeV. The water-cooled solution target insert was made of Ta and its solution holding capacity (1.6 mL) was reduced to enhance heat transfer. An isotopically enriched (99.23%) 1.7 M solution of (68)Zn nitrate in 0.2 N nitric acid was utilized in a closed target system. After a 30 min irradiation at 20 μA, the target solution was unloaded to a receiving vessel and the target was rinsed with 1.6 mL water, which was combined with the target solution. An automated module was used to pass the solution through a cation-exchange column (AG-50W-X8, 200-400 mesh, hydrogen form) which efficiently trapped zinc and gallium isotopes. (68)Zn was subsequently eluted with 30 mL of 0.5 N HBr formulated in 80% acetone without any measurable loss of (68)Ga. (68)Ga was eluted with 7 mL of 3 N HCl solution with 92-96% elution efficiency. The radionuclidic purity was determined using an HPGe detector. Additionally, ICP-MS was employed to analyze for non-radioactive metal contaminants. The product yield was 192.5 ± 11.0 MBq/μ·h decay-corrected to EOB with a total processing time of 60-80 min. The radionuclidic purity of (68)Ga was found to be >99.9%, with the predominant contaminant being 67Ga. The ICP-MS analysis showed small quantities of Ga, Fe, Cu, Ni and Zn in the final product, with (68)Ga specific activity of 5.20-6.27 GBq/μg. Depending upon the user requirements, (68)Ga production yield can be further enhanced by increasing the (68)Zn concentration in the target solution and extending the irradiation time. In summary, a simple and efficient method of (68)Ga production was developed using low energy cyclotron and a solution target. The developed methodology offers a cost-effective alternative to the (68)Ge/(68)Ga generators for the production of (68)Ga.

Objective: The existing solid target production method of radiometals requires high capital and operational expenditures, which limit the production of radiometals to the small fraction of cyclotron facilities that are equipped with solid target systems. Our objective is to develop a robust solution target method, which can be applicable to a wide array of radiometals and would be simply and easily adopted by existing cyclotron facility for the routine production of radiometals., Method: We have developed a simplified, solution target approach for production of (89)Zr using a niobium target by 14 MeV energy proton bombardment of aqueous solutions of yttrium salts via the (89)Y(p,n)(89)Zr nuclear reaction. The production conditions were optimized, following a detailed mechanistic study of the gas evolution., Results: Although the solution target approach avoided the expense and complication of solid target processing, rapid radiolytic formation of gases in the target represents a major impediment in the success of solution target. To address this challenge we performed a systematic mechanistic study of gas evolution. Gas evolution was found to be predominantly due to decomposition of water to molecular hydrogen and oxygen. The rate of gas evolutions varied >40-fold depending on solution composition even under the same irradiation condition. With chloride salts, the rate of gas evolution increased in the order rank Na