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19F标记的5-羟色氨酸的组织免疫测定

Tissue immunoassay for 19F-tagged 5-hydroxytryptophan.

作者信息

Dingman Sherry, Hurlburt Lara, Thomas Rhys, Guo Congyuan

机构信息

Marist College, Poughkeepsie, New York 12601, USA.

出版信息

J Immunoassay Immunochem. 2003;24(4):325-44. doi: 10.1081/IAS-120025771.

Abstract

A new tool for magnetic resonance, L-6-heptafluorobutyryl-5-hydroxytryptophan, was synthesized and investigated using an antibody to perfluoroalkyl moieties developed previously. To be useful as an imaging agent, the compound must cross the blood brain barrier and then be concentrated in vesicles in serotonergic neurons in order to accumulate in sufficient quantity for in vivo detection to be possible. The novel imaging compound was administered in ova to domestic chicks (Gallus domestics) to investigate the bioavailability and uptake dynamics of the compound in this model organism. Typical immunoassay methods were ineffective, so a new technique was developed which binds amines and amino acids to the walls of acid-functionalized cuvettes. The first study established the presence of higher quantities of the tags in neural and liver tissue than in heart tissue. A second study investigated regional differences, with the midbrain containing more tagged compounds than the frontal lobe sample, and the frontal lobe sample containing more than the occipital or cerebellum samples. These studies demonstrate that the compound follows the pathway of endogenous serotonin. A third study investigated uptake dynamics of the novel compound. Maximum concentration of the tagged molecule in the brain was achieved three days after injecting Incubation Day 14 eggs, suggesting that it bioaccumulates in vivo. This new immunoassay technique used to detect the novel compound in tissue samples demonstrated good repeatability.

摘要

一种用于磁共振的新工具——L-6-七氟丁酰基-5-羟基色氨酸被合成出来,并使用先前开发的针对全氟烷基部分的抗体进行了研究。要作为一种成像剂发挥作用,该化合物必须穿过血脑屏障,然后在血清素能神经元的囊泡中浓缩,以便积累到足够的量从而实现体内检测。将这种新型成像化合物经卵注射到家鸡(原鸡)体内,以研究该化合物在这种模式生物中的生物利用度和摄取动态。典型的免疫测定方法无效,因此开发了一种将胺和氨基酸结合到酸功能化比色皿壁上的新技术。第一项研究证实,神经组织和肝脏组织中的标记物含量高于心脏组织。第二项研究调查了区域差异,中脑含有的标记化合物比额叶样本多,而额叶样本含有的标记化合物比枕叶或小脑样本多。这些研究表明该化合物遵循内源性血清素的途径。第三项研究调查了这种新型化合物的摄取动态。在孵化第14天的鸡蛋中注射后三天,大脑中标记分子的浓度达到最高,这表明它在体内会生物蓄积。用于检测组织样本中新型化合物的这种新免疫测定技术显示出良好的重复性。

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