Abstract
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.
Highlights
IntroductionNamed vitamin B 1, is an essential nutrient that can be acquired only via diet
Thiamine, named vitamin B 1, is an essential nutrient that can be acquired only via diet
thiamine diphosphate (TDP) is the common coenzyme of the three key enzymes in glucose catabolism: pyruvate dehydrogenase and α-ketoglutarate dehydrogenase in the Krebs cycle that is responsible for producing ATP in mitochondria, and transketolase in pentose phosphate pathway that generates antioxidants and the substrates of biosynthesizing DNA, RNA, and fatty acid in cytosol [6]
Summary
Named vitamin B 1, is an essential nutrient that can be acquired only via diet. Thiamine deficiency (TD) is associated with some neuropsychological diseases, such. Wang et al EJNMMI Res (2020) 10:126 as Wernicke–Korsakoff syndrome, Alzheimer’s disease (AD), beriberi, Leigh syndrome, and so forth, and results in lactic acidosis, mitochondrial dysfunction, and energy deficits in brain, muscle, and heart, causing a broad range of clinical manifestations, such as anorexia, agitation, diminished tendon reflexes, ataxia, disturbance of consciousness, muscle pain, and heart failure. TDP is the common coenzyme of the three key enzymes in glucose catabolism: pyruvate dehydrogenase and α-ketoglutarate dehydrogenase in the Krebs cycle that is responsible for producing ATP in mitochondria, and transketolase in pentose phosphate pathway that generates antioxidants and the substrates of biosynthesizing DNA, RNA, and fatty acid in cytosol [6]. Some neuropsychological diseases are associated with abnormal thiamine metabolism, including Korsakoff–Wernicke syndrome and Alzheimer’s disease. In vivo detection of the status of brain thiamine metabolism is still unavailable and needs to be developed
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