68ga放射性标记荧光染料用于蛛网膜下腔出血潜在的无创多模态成像。

IF 4.4 Q1 CHEMISTRY, INORGANIC & NUCLEAR
Jona Wilhelm Gerhards, Laura Schäfer, Daniel Kang, Ute Lindauer, Susanne Lütje, Felix Manuel Mottaghy, Tobias Schmidt, Andreas Theodor Josef Vogg
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引用次数: 0

摘要

背景:动脉瘤性蛛网膜下腔出血(aSAH)是一种独特的中风类型,主要由脑动脉瘤破裂引起。aSAH的潜在机制尚不完全清楚,这促使了该领域的持续研究。最近对血管周围系统的调查显示,在测量期间,染料Alexa Fluor™594的分布受到干扰。为了进一步研究这种分布异常,建议用放射性核素标记染料,利用正电子发射断层扫描技术对大鼠进行生物动力学跟踪,以增强成像和分析。结果:螯合剂结合后的荧光染料Alexa Fluor™594成功地以无载体添加形式用正电子发射放射性核素68Ga(III)标记。最初,使用NODA-GA-NHS酯与Alexa Fluor™594 1,5-二氨基戊烷的氨基反应,便于随后用68Ga进行放射性标记。Alexa Fluor™594螯合剂偶联物的形成以及放射性标记,作为反应时间和温度的函数进行了研究。考虑到68Ga半衰期短,在潜在的动物实验中,有必要将反应温度从室温提高到80℃,以优化反应条件。建立了最佳标记条件,使放化产率达到85%。对n.c.a. [68Ga]Ga-NODA-GA-Alexa Fluor™594进行分离纯化,杂质残留量低于3%。结论:这种实验方法成功地产生了所需的放射性标记染料,现在可用于动物研究,有可能为深入了解aSAH的机制提供更好的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
68Ga-radiolabeled fluorescent dye for potential non-invasive multimodal imaging of subarachnoid hemorrhage.

Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a distinct type of stroke, primarily caused by the rupture of a brain aneurysm. The underlying mechanisms of aSAH remain incompletely understood, prompting ongoing research in this area. Recent investigations into the perivascular system revealed a distribution disturbance of the dye Alexa Fluor™ 594 during measurements. To further investigate this distribution anomaly, it is proposed to label the dye with a radionuclide for biokinetic tracking in rats by means of positron emission tomography for enhanced imaging and analysis.

Results: The fluorescent dye Alexa Fluor™ 594 after chelator conjugation was successfully labeled with the positron-emitting radionuclide 68Ga(III) in a no-carrier-added form. Initially, the NODA-GA-NHS ester was employed to react with the amino group of Alexa Fluor™ 594 1,5-diaminopentane, facilitating subsequent radiolabeling with 68Ga. The formation of the Alexa Fluor™ 594-chelator conjugate, as well as the radiolabeling, were investigated as a function of reaction time and temperature. For potential animal experiments, it was necessary to increase the reaction temperature from room temperature to 80 °C to optimize the reaction conditions, given the short half-life of 68Ga. Optimal labeling conditions were established, achieving a radiochemical yield of > 85%. Separation and purification of n.c.a. [68Ga]Ga-NODA-GA-Alexa Fluor™ 594 were conducted, with impurities remaining below 3%.

Conclusions: This experimental approach successfully yields the desired radiolabeled dye, which is now available for animal studies, potentially offering enhanced insight into the mechanisms of aSAH.

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来源期刊
CiteScore
7.20
自引率
8.70%
发文量
30
审稿时长
5 weeks
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