Radiosynthesis of novel 68ga-labelled-α-cyclodextrin for pet imaging

Abstract

Cyclodextrins (CDs) are cyclic oligosaccharides composed of glucose units linked by α-1,4 glycosidic bond. CDs are commonly used as pharmaceutical excipients and they offer versatile benefits in various industries. Recently, CDs have been promising for the application of medical imaging, especially nuclear medicine imaging. Herein, we aim to radiosynthesize 68Ga-alpha-cyclodextrin (68Ga-αCD) by directly radiolabeling Ga-68 to αCD. Briefly, Ga-68 was eluted, mixed with αCD solution and heated at 100 °C for 20 min. Subsequently, the reaction was allowed to cool down at room temperature. The resulting 68Ga-αCD was characterized using mass spectrometry (MS) and elucidated by in silico computational studies. Radioactivity was measured using instant thin layer chromatography. The radiochemical purity (RCP) was calculated. The pH of the resulting solution was measured using a pH meter. The radiosynthesis process was then optimized and purified to increase the RCP of 68Ga-αCD. The radiostabilizers, i.e., sodium ascorbate or ascorbic acid, were selected, various concentrations of αCD solutions (0.25–5 mg/ml) and αCD polymer were included to optimize the process and C-18 cartridge was employed to purify 68Ga-αCD solution. Initially, the RCP of 68Ga-αCD is very low (0.24 ± 0.03%). Upon the optimization using sodium ascorbate as radiostabilizer together with 1 mg/ml αCD solution and further purification using C-18 cartridge, the RCP is significantly increased. Ultimately, we have successfully achieved an RCP of 18.4 ± 1.1%. Subsequently, miconazole or cyclosporin A was introduced into the αCD cavity prior to radiolabeling, but no significant impact on the binding affinity between Ga-68 and αCD was observed. This is subsequently confirmed by MS and computational studies that the stoichiometry ratio of Ga-68 and αCD is 1:1 complex and binding site of Ga-68 is on either primary or secondary rim of αCD.