Multiparametric Labeling Optimization and Synthesis of 68Ga-Labeled Compounds Applying a Continuous-Flow Microfluidic Methodology

• Published in: Journal of flow chemistry Vol. 6; no. 2; pp. 86 - 93
• Main Authors: Máté, Gábor, Szikra, Dezső, Šimeček, Jakub, Szilágyi, Szandra, Trencsényi, György, Wester, Hans-Jürgen, Kertész, István, Galuska, László
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.04.2016
• Subjects: Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Green Chemistry; Industrial Chemistry/Chemical Engineering; Inorganic Chemistry; Nanochemistry; Organic Chemistry; Gallium; positron emission tomography; RGD conjugates; microfluidics; chelators
• ISSN: 2062-249X; 2063-0212
• DOI: 10.1556/1846.2016.00004

The synthesis and functional evaluation of a wide variety of radiolabeled chelator—biomolecule conjugates with high specific activity and radiochemical purity are crucial to development of personalized nuclear medicine. An excellent platform technology for achieving this objective involves use of generator-produced positron emission tomography (PET)-radionuclide 68 Ga. Currently, applied manual methodology for optimization and development for new labeling techniques offers only slow screening with relatively high precursor consumption. A capillary-based microfluidic synthesis module with online high-performance liquid chromatography (HPLC) was constructed for the optimization of reaction parameters of 68 Ga-PET tracers. This approach enables performance of 68 Ga-labeling reactions in 10 μL volumes, followed by sample analysis. The high-throughput capacity of the system allows very rapid optimization. The optimal pH and ligand concentration from the experiments were utilized directly to the production of 68 Ga-NODAGA-(RGD) 2 and 68 Ga-NOPO-RGD. Applying optimal parameters to production of these aforementioned radiopharmaceuticals allowed their synthesis with high radiochemical purity (over 95%) and with surprisingly negligible retention of residual activity in the system.