Synthesis Of ⁶⁸Ga-citrate And Preliminary Clinical Translation Of ⁶⁸Ga-citrate Imaging In Evaluation Of Inflammatory Bowel Disease

Objective:to synthesize Ga citrate simply, validate its qualities in vitro and evaluate the possibility of detecting bacteria infection and inflammation with 68Ga citrate.The objective of this study was to differentially diagnose UC and CD by 68Ga citrate PET and 18F-FDG PET.Materials and methods:Sodium citrate (0.1M,0.2ml) was added into newly eluted 68Ga (370MBq,0.6ml) with 0.05 M HCl from 68Ge/68Ga and incubated at room temperature for 15min. The labeled product was diluted with saline and loaded on ITLC-SG strips to determine the radiochemical purity. An infection was induced in ICR mice by injecting Staph A in the right thigh muscle.68Ga-Citrate (3.7 MBq/mouse) was injected intravenously and the PET images were acquired in normal mice and inflammation model mice at different time-points.After giving informed consent,34 patients with suspected inflammatory bowel disease were prospectively studied.18F-FDG PET/CT was performed at 60 min and at 120 min after injection of F-FDG. 68Ga-citrate PET/CT was performed at 30 min and at 90 min after injection of 68Ga-citrate.Within a 2-week window, endoscopy was underwent. First, we evaluated 1 F-FDG or 6 Ga-citrate uptake visually and semi-quantitatively using standardized uptake values (SUVmax). Second, we estimated the difference between early and delayed SUVmax to evaluate the change of tracers in the lesions with CD and UC. Third, we estimated the difference between normal colon and lesion using standardized uptake values (SUVmax) of the patients with CD and UC. The efficacy of each parameter was analyzed with spearman test. Results:68Ga-citrate was labeled with >99% yield and purity within 15 minutes and can be used for PET imaging without further purification. In normal mice,68Ga-citrate visualized heart and excreted through bladder.68Ga-citrate uptake was increasingly higher at the infection lesion from 20 min to 120 min post injection. By statistical analysis, Crohn’s disease and ulcerative colitis, either early or delayed imaging of 68Ga-citrate.There was no significant diagnostic value. But there was statistically significant in either early or delayed imaging of 18F-FDG PET (p=0.0207,p=0.0017,respectively). There was no difference between moderate activity of Crohn’s disease and moderate activity of ulcerative colitis in the imaging of 68Ga citrate.Conclusion:68Ga-citrate was prepared in a simplified method. The preliminary data showed that 68Ga-citrate was capable of detecting inflammation caused by Staph A infection in mice.68Ga-citrate and 18F-FDG PET were useful to evaluate the lesion of colon. There was no significance in the disease of colon in the imaging of 68Ga-citrate, but dual-time-point 18F-FDG PET/CT imaging may help to differentiate active UC from CD in our study.