Extending the shelf life of ⁶⁸Ge/⁶⁸Ga generators via preconcentration of [⁶⁸Ga]GaCl₃ for preclinical application

⁶⁸Ga-labeled tracers are increasingly important for PET imaging and as companion diagnostics with new therapeutic radiopharmaceuticals. The ⁶⁸Ge/⁶⁸Ga generator is a common source for clinical and preclinical ⁶⁸Ga-tracer production; however, its shelf life and efficiency are critical because of the high cost of generator replacement. This study assessed whether preconcentration of [⁶⁸Ga]GaCl₃ using strong cation exchange (SCX) resin can increase yield, apparent molar activity (AMA) and also extend generator shelf-life for preclinical applications.

A ⁶⁸Ge/⁶⁸Ga generator (1.8 GBq at purchase, 14-18 months old) was used. Direct elution involved elution of [⁶⁸Ga]GaCl₃ in 0.1 M HCl, followed by addition to a DOTA-conjugated affibody in acetate buffer (pH 4.6). Preconcentration involved trapping [⁶⁸Ga]GaCl₃ on a SCX (Chromafix PS-H⁺) cartridge, rinsing, and eluting with 0.12 M HCl in 5 M NaCl (300-500 µL), followed by radiolabeling. Radiolabeling was performed at 75-80 °C for 15 min, the products were purified using a NAP-5 column, and the purity was assessed by high-performance liquid chromatography (HPLC). The SCX cartridge trapping efficiency was > 99%, with a elution efficiency of 95.2 ± 1.2% (n = 8). For direct elution, the decay-corrected radiochemical yield (RCYdc) was 78.7 ± 1.5% (n = 3), the AMA was 5.6 ± 0.4 MBq/nmol, and the radiochemical purity (RCP) was 95.3 ± 0.6%. For preconcentration, RCY_dc was 69.0 ± 10.0% (n = 3), AMA was 12.6 ± 2.1 MBq/nmol, and RCP was 95.7 ± 3.0%.

The preconcentration technique doubled the product yield and AMA, and extended the shelf life of the generator by 9-12 months for preclinical applications. Preconcentration of [⁶⁸Ga]GaCl₃ using SCX resin is a robust, cost-effective method for maximizing ⁶⁸Ga recovery and increasing the radiotracer yield and AMA, especially with older generators. This approach extends generator shelf-life, supports sustained preclinical research, and reduces radioactive waste and operational costs.