Ready-For-Use-module full automated and standardized production of 68Ga-DOTATOC

Introduction: Currently, the somatostatin imaging using DOTA conjugated peptides like DOTA-TOC, -NOC and -TATE are the common applications. Different 68Ge/68Ga generator systems and synthesis modules are described separately. We describe a new full automated and standardized production of 68Ga-DOTATOC. Methods: The module has to fit with components like the pre-conditioned C18 purifications cartridge and the DOTATOC precursor solute in HEPES buffer. The generator was fractionally eluted in time steps of 30 sec. An elution profile was created and the time frame of the middle fraction was adjusted with the basis software and the flow rate of the peristaltic pump. The reaction vial was charged with 30 μg DOTATOC solved in 100μl HEPES buffer (150-200mg / 0.1 ml) and placed in the heating block. The generator was eluted with 0.6 N HCl and the reaction volume (~ 1ml) was collected at the reaction vial after switching the valves V2 and V3 for 40 s. The labeling was performed under 95°C for 12 min at pH 3.5-4. Purification was achieved by injecting the reaction mixture onto the C18cardridge, washing with 1,5 ml H2O and 10 ml air. The 68Ga-DOTATOC was transferred over a sterile filter to the product vial by elution with 1 ml ethanol and 9 ml of saline. Results: The tin dioxide generator we used was specified with an elution yield in 5 ml not less than 80%. The rule of thumb prognosticates a durability of 200 elutions or 10 month. After ~ 70 elution the yield of our systems fall below the value of 80%. The typical overall elution, labeling and purification procedure took less than 25 min.The non-ionic buffer HEPES was most effective and the optimal amount was ~ 160 mg. Using 33 μg (23 nmol),the labeling yield was 60%-65% and their radiochemical purity was > 97%. Conclusion: The combination of a 68Ge/68Ga generator, produced under cGMP guidelines and a "Ready for use" automated module allows a standardized production with high radiochemical yields for 68Ga-DOTATOC. This combination of both will provide the user with facile and reliable package for the preparation in routine clinical applications, especially und the aspect of cGLP and cGMP