^11C-[2-甲氧基]-左旋千金藤啶碱的制备及生物学评价

Synthesis of n C-M-1-SPD and its biodistribution in rats

目的探讨合成^11C-[2-甲氧基]-左旋千金藤啶碱（^11C M—l—SPD）的方法及其在大鼠体内的生物学分布。方法使用”C-三氟甲基磺酰甲烷（CH3-triflate）进行^11C标记M—l—SPD，采用“反应瓶”法制备^11C—M-l-SPD。SD大鼠25只，均为雄性，使用随机数字法将其分为5组，经尾静脉注入^11C—M—z—SPD0．2ml（22．2MBq），分别于5、15、30、60和90min后断头处死，取出肺、心、肝、脾、胃、肠、肾、肌肉、脑等组织器官。于上述时间点取出脑额叶、顶叶、颞叶、枕叶、小脑、海马、纹状体、丘脑、脑干，测质量。用γ计数仪测定各组织放射性计数，计算湿组织％ID／g。采用SPSS15．0软件进行方差分析。结果^11C—M—z—SPD放化合成时间约为15rain，时间校正后放化产率为16％～34％；^11C．M—Z—SPD注射液为无色，pH值约为6．5，放化纯大于95％^11C—M—z＋SPD在体内吸收迅速，分布广泛，以肝、肾、心、脑、肺分布最多。静脉注入”C—M—Z—SPD5min后在各组织内放射性分布达到高峰，5min后各组织呈明显下降趋势，给药后60min，各脏器内放射性明显下降。^11C—M—z—SPD主要经肝、肾代谢，肝、肾组织在注药后5min放射性分布分别为（1．484±0．350）％ID／g和（1．323±0．153）％ID／g，90min分别为（0．478±0．059）％ID／g和（0．394±0．165）％ID／g。在胃、脾、肠、肌肉等组织放射性分布较少。各脑区内放射性分布5min达到高峰，各脑区放射性分布差异无统计学意义（F：0．054、0．690、0．333、0．487和0．686，P均〉0．05）。结论使用^11C模块自动化制备^11C—M．f—SPD简便快速，有望用于l-SPD的活体PET显像。

Objective To explore the synthesis method of ^11C-[ 2-O-CH3 ] -l-stepholidine（ H C-M-1- SPD） and evaluate its biodistribution in rats. Methods H C-CH3-triflate was bubbled into the reactor of an automated remotely controlled radiosynthesizer module, which contained reaction materials in a V-tube. Twenty-five SD rats were randomly divided into 5 groups. Different organs （lung, heart, liver, spleen, stom- ach, intestine, kidney, muscle and brain） were excised at different time points （5, 15, 30, 60 and 90 rain） post-injection of H C-M-I-SPD （0.2 ml, 22.2 MBq）. Then the counts per minute of each organ were measured, and the % ID/g was calculated. Biodistribution in different regions of the brain （ frontal lobe, apical lobe, temporal lobe, occipital lobe, cerebellum, hippocampus, striatum, thalamencephalon and brain stem） was further evaluated. Analysis of variance was used for data analysis with SPSS 15.0. Results The synthesis time of ^11C_M_l_SPD was 15 min. The overall radiochemical yield was 16%-34%. The product was colorless in a pH value of 6.5, and the radiochemical purity was more than 95%. Five min post-injection, the biodistribution of 11C-M-I-SPD reached high levels in the liver, kidney, heart, brain and lung, and then dropped quickly. Levels decreased clearly in most organs at 60 min after administration. The liver and kidney were the main excretory organs. The biodistribution of HC-M-I-SPD in liver and kidney was （1. 484±0.350） % ID/g and （1. 323 ± 0. 153 ） % ID/g at 5 min after administration and went down to （0. 478± 0. 039 ） % ID/g and （0. 394 ±0. 165 ） % ID/g at 90 min, respectively. Lower radioactivity was found in the stomach, spleen, intestine and muscle. The uptake of 11C-M-/-SPD in the brain reached a peak at 5 min after injection, and there was no significant differences in the brain regions （ F = 0. 054, 0. 690, 0. 333, 0. 487, 0.686, all P 〉0.05）. Conclusion The automatic synthesis of I xC-M-l-SPD is simple and fast, which provides the feasibility of its usage in PET imaging in vivo.