A novel PET tracer 18F-deoxy-thiamine: synthesis, metabolic kinetics, and evaluation on cerebral thiamine metabolism status

EJNMMI Research

Lei Sheng¹  Chunjiu Zhong²  Changpeng Wang²  Shaoming Sang²  Lirong Jin²  Yuefei Zou³  Hongzhao Ma³  Zhihong Xu³  Siwei Zhang³  Yuan Gui³  Donglang Jiang⁴  Yihui Guan⁴ 

[1] Department of Clinical Pharmacology, Zhongshan Hospital, Fudan University, 200032, Shanghai, China;Department of Neurology, Zhongshan Hospital, State Key Laboratory of Medical Neurobiology and Institute of Brain Science, Fudan University, 200032, Shanghai, China;Jiangsu Huayi Technology Co., Ltd., 215519, Jiangsu, China;PET Center, Huashan Hospital, Fudan University, 200235, Shanghai, China;

关键词: Thiamine;    F-deoxy-thiamine;    Tracer;    Positron emission tomography;   

DOI  :  10.1186/s13550-020-00710-5

来源: Springer

【 摘 要 】

BackgroundSome neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. However, in vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed.MethodsA novel PET tracer of 18F-deoxy-thiamine was synthesized using an automated module via a two-step route. The main quality control parameters, such as specific activity and radiochemical purity, were evaluated by high-performance liquid chromatography (HPLC). Radiochemical concentration was determined by radioactivity calibrator. Metabolic kinetics and the level of 18F-deoxy-thiamine in brains of mice and marmosets were studied by micro-positron emission tomography/computed tomography (PET/CT). In vivo stability, renal excretion rate, and biodistribution of 18F-deoxy-thiamine in the mice were assayed using HPLC and γ-counter, respectively. Also, the correlation between the retention of cerebral 18F-deoxy-thiamine in 60 min after injection as represented by the area under the curve (AUC) and blood thiamine levels was investigated.ResultsThe 18F-deoxy-thiamine was stable both in vitro and in vivo. The uptake and clearance of 18F-deoxy-thiamine were quick in the mice. It reached the max standard uptake value (SUVmax) of 4.61 ± 0.53 in the liver within 1 min, 18.67 ± 7.04 in the kidney within half a minute. The SUV dropped to 0.72 ± 0.05 and 0.77 ± 0.35 after 60 min of injection in the liver and kidney, respectively. After injection, kidney, liver, and pancreas exhibited high accumulation level of 18F-deoxy-thiamine, while brain, muscle, fat, and gonad showed low accumulation concentration, consistent with previous reports on thiamine distribution in mice. Within 90 min after injection, the level of 18F-deoxy-thiamine in the brain of C57BL/6 mice with thiamine deficiency (TD) was 1.9 times higher than that in control mice, and was 3.1 times higher in ICR mice with TD than that in control mice. The AUC of the tracer in the brain of marmosets within 60 min was 29.33 ± 5.15 and negatively correlated with blood thiamine diphosphate levels (r = − 0.985, p = 0.015).ConclusionThe 18F-deoxy-thiamine meets the requirements for ideal PET tracer for in vivo detecting the status of cerebral thiamine metabolism.

【 授权许可】

CC BY