Efficient GMP production of ⁶⁸Ga-peptides on a commercial synthesizer using a ⁶⁸Ge/⁶⁸Ga generator with direct labelling

Objectives The aim of this work is to demonstrate that GMP production of ⁶⁸Ga-DOTA-NOC and ⁶⁸Ga-PSMA-11 could be achieved through the use of a cassette-based synthesizer (Synthera^®, IBA, Louvain-la-Neuve, Belgium) in combination with a new commercial ⁶⁸Ge/⁶⁸Ga generator (Galli Eo^TM, IRE-Elit, Fleurus, Belgium) where no pre-purification is required. In this way, direct labelling is possible streamlining the production process with higher radiochemical yields while maintaining the high quality of the final product.

Methods The generator outlet is connected to an unmodified FDG-type disposable cassette with the appropriate reagent set and ancillaries. The automated process starts with a vacuum-assisted elution using only 1.1 mL of a 0.1 M HCl solution from the generator integrated reservoir. Since pre-purification is not required, ⁶⁸Ga activity is directly sent to the reaction vessel.DOTA-NOC labeling uses a solution of 50 µg peptide in 1 mL 250 mM acetate buffer at pH 5 which is then is heated at 120°C for 5 min. Afterwards, the reaction bulk is loaded onto a HLB Oasis^® Light HLB cartridge and washed with 10 mL of water. ⁶⁸Ga-DOTA-NOC is then eluted with 1 mL of EtOH/water 65:35 v/v mix followed by 1 mL of saline 0.9% and collected through a 0.22 µM Millex®-GV filter into a sterile vial containing 8 mL of saline 0.9%. PSMA-11 labeling employs a solution of 10 µg peptide in 1 mL 1.5 M acetate buffer at pH 4.5 which is then heated at 95°C for 5 min. After the reaction bulk is loaded onto a Sep-pak^® Light C18 cartridge and washed with 10 mL of water. ⁶⁸Ga-PSMA-11 is then eluted with 2 mL of EtOH/water 1:1 v/v mixture followed by 2 mL of phosphate buffered saline (PBS) and collected through a 0.22 µM Millex®-GV filter into a sterile vial containing 6 mL of PBS.

Results Both ⁶⁸Ga-DOTA-NOC and ⁶⁸Ga-PSMA-11 are produced in <20 min (< 13 min for PSMA) with high decay-corrected (d.c.) radiochemical yields of 81.5±5.2 % and 97.4±2.5 %, respectively. Reported process times include generator elution and formulation. In both cases, final products show high radiochemical purity (TLC > 97 % and 99 %, respectively).

Conclusions Fast and efficient labelling of ⁶⁸Ga-DOTA-NOC and ⁶⁸Ga-PSMA-11 have been achieved using a commercial synthesizer and a ⁶⁸Ge/⁶⁸Ga generator without pre-purification prior to the labelling. The low elution volume and high purity of the generator eluate (no need for fractionation or post-elution purification) supported the direct labelling without compromising the radiochemical yields and the quality of final product.