cGMP Synthesis of 68Ga-PSMA-HBED from Cyclotron Produced 68GaCl3

198 Objectives: To synthesize 68Ga-PSMA-HBED in a cGMP facility from cyclotron produced 68GaCl3 as an alternative to 68Ga/68Ge generator for routine clinical use. Methods: Leveraging a high production yield of 68Ga in a liquid cyclotron target (BMLT-2)1-2, we synthesized 68Ga-PSMA-HBED under cGMP using cyclotron produced 68GaCl3. A solution of 1.5 M 68Zn-nitrate in 1.2 N nitric acid was employed for proton irradiation at 40 µA current for 60 min to produce 68Ga(NO3)3. The 68Ga(NO3)3 was purified in two steps using in-house synthesized hydroxamate resin (100 mg) followed by trapping of 68Ga as [68GaCl4]- on an anion exchange resin (AG-1X-8, 400 mg) using an automated radiochemistry module (Trasis All-in-One)2-3. Finally, 68GaCl3 was eluted in 2 mL of water and transferred to a reactor vial preloaded with 5 ug of PSMA-HBED precursor in 3M sodium acetate. Radiolabeling was carried out at 100 oC for 10 min followed by trap-and-release from a C-18 Sep-Pak to remove free 68Ga before elution of 68Ga-PSMA-HBED with 2 mL ethanol-water (50:50) followed by 10 mL sterile 0.9% NaCl. The 68Ga-PSMA-HBED product underwent standard routine radiopharmaceutical quality control tests, including physical appearance, pH, filter integrity, radionuclidic identity, molar activity, endotoxin, sterility, radiochemical and radionuclidic purities. Results: 68Ga-PSMA-HBED was produced in 54.8-62.8% yield, corrected to end of bombardment (EOB). The total time of 68Ga isotope purification and labeling of PSMA-HBED as 68Ga-PSMA-HBED was 80-86 min post EOB. The in-hand 68Ga-PSMA-HBED for clinic use was 1.78-3.18GBq (48-86 mCi, uncorrected). The 68Ga-PSMA-HBED product passed all the quality control parameters for a cGMP synthesis. The high labeling yield demonstrated successful isotope purification of 68Ga from 68Zn raw material. Conclusions: Cyclotron produced 68GaCl3 was successfully utilized to synthesize 68Ga-PSMA-HBED in good yield and provides an attractive alternative to 68Ga/68Ge generator for routine clinical use. Currently, 68Ga-PSMA-HBED is being clinically evaluated in comparison to 11C-Choline. Cyclotron produced 68GaCl3 can also be used to synthesize 68Ga-DOTATATE and other 68Ga labeled radiopharmaceuticals. Research Support: This project was funded by Center for Individualized Medicine and Department of Radiology, Mayo Clinic Rochester MN. References: Pandey et al. Cyclotron production of 68Ga via the 68Zn (p, n) 68Ga reaction in aqueous solution American journal of nuclear medicine and molecular imaging 2014, 4 (4), 303 Pandey et al. Effects of Solution Composition and Irradiation Parameters on 68Ga Production in a Liquid Target using Cyclotron J Nucl Med 2018 59:665 and Pandey et al. WTTC 2018 Proceedings (http://wttc.triumf.ca) Pandey et al. WTTC 2016 Proceedings (http://wttc.triumf.ca): 10-11 and Pandey et al Automated Processing of Cyclotron Produced 68Ga Using Hydroxamate Resin J Nucl Med 2017 58:3330