四种潜在的脑pH成像剂——硒标记叔胺的合成与组织分布

Synthesis and tissue distribution of four Se-labeled tertiary amines, potential brain pH imaging agents.

作者信息

Plenevaux A, Cantineau R, Brihaye C, Lemaire C, Christiaens L, Guillaume M

机构信息

Cyclotron Research Center, Liège University, Belgium.

出版信息

Int J Rad Appl Instrum B. 1990;17(6):601-7. doi: 10.1016/0883-2897(90)90136-o.

DOI:10.1016/0883-2897(90)90136-o

PMID:2254097

Abstract

Four new tertiary amines: bis(3-N,N-dimethyl aminopropyl)selenide (PROMOSE), bis(3-N-(morpholino)propyl)selenide, N-methyl-selenomorpholine and N-phenyl-selenomorpholine structurally related to MOSE proposed by Kung and Blau, have been labeled through a radiochemical procedure suitable for both 75Se and 73Se. The radiochemical yields of the carrier added synthesis ranged between 64 and 85% for the four 75Se labelings and was 64% EOB time corrected for [73Se]PROMOSE. The chemical and radiochemical purities were higher than 99% after chromatographic purifications. The n-octanol/phosphate buffer partition coefficients (P) were measured at various pH (6.5-8) for each compound and the tissue distributions of PROMOSE in rats were also carried out. The experimental results showed a good correlation between the P = f(pH) function and the in vivo behaviour of the considered compound. PROMOSE was selected for further investigations as a brain pH indicator.

摘要

四种新的叔胺

双（3-N，N-二甲基氨基丙基）硒化物（PROMOSE）、双（3-N-（吗啉代）丙基）硒化物、N-甲基-硒代吗啉和N-苯基-硒代吗啉，其结构与Kung和Blau提出的MOSE相关，已通过适用于75Se和73Se的放射化学程序进行标记。对于四种75Se标记，载体添加合成的放射化学产率在64%至85%之间，经EOB时间校正后，[73Se]PROMOSE的放射化学产率为64%。色谱纯化后，化学纯度和放射化学纯度均高于99%。测定了每种化合物在不同pH值（6.5 - 8）下的正辛醇/磷酸盐缓冲液分配系数（P），并对大鼠体内PROMOSE的组织分布进行了研究。实验结果表明，P = f(pH)函数与所考虑化合物的体内行为之间具有良好的相关性。PROMOSE被选为进一步研究的脑pH指示剂。