Optimal buffer choice of the radiosynthesis of (68)Ga-Dotatoc for clinical application

Abstract

Objectives: (68)Ga-Dotatoc has become the PET radiopharmaceutical of choice for the diagnosis and treatment follow-up of neuroendocrine tumours. (68)Ga-Dotatoc is prepared on-site through a so-called magisterial preparation. The use of an appropriate buffer during the radiolabelling step is essential to maximize the labelling yield and the specific activity. Such a buffer should be nontoxic, able to buffer in the pH range of 3.5-5.0, not compete with gallium ions and preferentially have a weak metal complexing capacity to avoid the formation of colloidal gallium. In addition, the buffer should be allowed for human use. In view of the high radiation dose to the operator when manually handling (68)Ga, especially to the extremities, we also tested the buffers in a semi-automated system.

Methods: HEPES, acetate, succinate, Tris, glutamate, lactate, oxalate and tartrate were tested as potential buffers in the manual radiosynthesis of (68)Ga-Dotatoc. Temperature, heating time and substrate concentration were optimized.

Results: Buffers based on HEPES, acetate and succinate were found to be the most appropriate. Optimal labelling yields were achieved with a 5-min heating time for the manual synthesis and 8 min for a semi-automated system, whereas the optimal amount of Dotatoc was 30 and 40 microg, respectively.

Conclusion: Although the use of HEPES, acetate and succinate as buffering substances yielded comparable results, only acetate is currently recognized as a substance for pharmaceutical use and also for human use. Therefore, acetate buffer should be used for (68)Ga-Dotatoc synthesis. The semi-automated system allowed for a shorter radiosynthesis time, thereby increasing the overall yield.