Production optimization of 68Ga-DOTA-NOC for routine synthesis

1005 Objectives The development of a simple and reproducible process for labelling peptides with generator produced Gallium 68 (68Ga) is of critical importance for their widespread clinical use in PET. In this work, we describe a simple and reproducible process using a commercial synthesizer (IBA Synthera®) coupled with a standard 68Ge/68Ga generator (iThemba LABS). Test and synthesis method sequences were developed and implemented. Disposable cassettes were adapted from those used for FDG. Methods The generator is slowly eluted with 5-7mL of 0.6M HCl onto a cation exchange column (Strata X-C). 68Ga is retained and other impurities, such as 68Ge breakthrough, pass through the column. 68Ga is then eluted with 800 µL of 98% acetone/0.05M HCl solution into a reactor containing 30µg of the DOTA-NOC peptide in 1mL of buffer solution. The reaction mixture is heated for 15 minutes at 105 C. The mixture is then transferred to a Sep Pak® Light C18 purification cartridge and washed with 10ml of deionized water. 68Ga DOTA-NOC is then eluted with 0.5mL of EtOH and 9.5mL of 0.9% NaCl and sterile filtered via a 0.22µm filter. The final product is tested for chemical and radiochemical purity (HPLC), pH and residual solvents (GC). Results 68Ga DOTA-NOC was successfully synthesized in about 25 minutes with 89.7±3.9 % of decay corrected RCY. Purification, formulation and sterile filtration were done with >98% yields using a C18 cartridge eluted with 0.5 mL of EtOH. The radiochemical purity of the final labelled product was >99%, pH 5-7 and there were no residual solvents in addition to ethanol ( Conclusions Labelling of peptides with 68Ga was successfully obtained with the automated process developed using a commercial synthesizer with good radiochemical yields and suitable quality parameters. The process can easily be adapted for the labeling of other peptides and for other radiometals (e.g. 177Lu).