CNS & neurological disorders drug targets · 2023
Bis-iodine-labeled Curcumin as a Potential CT Imaging Agent for β-amyloid Plaques in the Brain.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Dai Yaqian, Peng Liduo, Tian Xiaoyan, Wu Xingwang, Xu Yuanhong, Jiang Taoshan, Qiao Jinping
Аннотация
BACKGROUND: Alzheimer's disease (AD) is one of the most common causes of dementia, affecting many old people.
OBJECTIVES: By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD.
METHODS: We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments.
RESULTS: In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, Kd values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD50 was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection.
CONCLUSION: All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.
OBJECTIVES: By designing and synthesizing intracerebral imaging probes, we tried to provide a new solution for the early diagnosis of AD.
METHODS: We designed and synthesized bis-iodine-labeled curcumin, and verified its performance through in vivo and in vitro experiments.
RESULTS: In this study, bis-iodine-labeled curcumin (7, BICUR) was synthesized. In the in vitro mass spectrum binding assay, Kd values of BICUR with Aβ1-40 and Aβ1-42 aggregates were 46.29 nM and 64.29 nM, respectively. Aβ plaques in AD brain adjacent sections were positively stained by BICUR, which was similar to some other curcumin derivatives. The Log P value of BICUR was 1.45. In the biodistribution experiment, BICUR showed the highest initial brain uptake (5.87% compared to the blood concentration) two minutes after the tail vein injection and rapid clearance from the mouse brain. In the acute toxicity experiment, BICUR showed low toxicity, and the LD50 was >100 mg/kg. Moreover, BICUR showed a high stability in vitro (86.68% unchanged BICUR after incubation for 120min in mouse brain homogenate). Besides, BICUR produced an enhanced CT imaging effect that could be sensitively detected in vitro, but it also showed an obvious differentiation from surrounding tissues after intracerebral injection.
CONCLUSION: All results suggested that BICUR could probably act as a targeted CT imaging agent for Aβ plaques in the brain.