新型骨显像剂^(99)Tc^m-BIPrDP的制备及其反应动力学研究  

Preparation and Reaction Kinetics of a New Bone Imaging Agent ^(99)Tc^m-BIPrDP

作　　者：张姝[1,2] 罗世能[2,1] 邱玲[2] 林建国[2] 夏咏梅 

机构地区：[1]江南大学化学与材料工程学院,江苏无锡214122 [2]江苏省原子医学研究所卫生部核医学重点实验室江苏省分子核医学重点实验室,江苏无锡214063

出　　处：《同位素》2011年第4期205-211,共7页Journal of Isotopes

基　　金：国家自然科学基金资助项目(20801024);江苏省自然科学基金资助项目(BK2009077);江苏省卫生厅科研项目(H200963)

摘　　要：以2-丁基咪唑为原料,经过N-烷基化、酯水解和磷酰化三步反应,合成了一种新型双膦酸配体1-羟基-3-(2-丁基-1H-咪唑-1-基)丙烷-1,1-双膦酸(BIPrDP),目标产物和中间体经过元素分析、质谱、核磁共振氢谱进行了结构鉴定。在SnCl2还原下,用Na99TcmO4对BIPrDP进行标记,得到一种新型骨显像剂99Tcm-BI-PrDP,进而对99Tcm-BIPrDP进行反应动力学研究。在40、50、60、70、80和90℃时的反应速率常数k分别为0.018 3、0.020 7、0.024 1、0.027 0、0.028 8和0.031 9。温度与反应速率常数k的关系为lnk=-1 267.1×1/T+0.055(r2=0.990 2),反应活化能Ea=10.53kJ.mol-1,远低于一般化学反应活化能(典型值20～150kJ.mol-1),表明99Tcm-BIPrDP的制备反应较容易进行。同时,通过测定不同温度下的标记率RLY可得RLY与温度的关系:ln[RLY/(1-RLY)]=-6 218.4/T+19.84。为使标记率大于90%,反应温度必须高于79.31℃。A new diphosphonic acid ligand, 1-hydroxy 3-（2-butyl-lH-imidazol-l-yl）propane- 1,1-diyldiphosphonic acid （BIPrDP）, was prepared from the starting material 2-butyl-1H- imidazole by three steps of reactions. N-alkylation, ester hydrolysis and phosphoric acid acylation. The structures of the intermediate and target compounds were identified by elemental analysis, MS and 1H-NMR. BIPrDP was directly labeled by Na99TcmO4 in the presence of the reducing agent SnCl2 to afford a new bone imaging agent ^99Tc^m-BIPrDP. The kinetics of the labeling reaction between BIBrDP and ^99TcmO4- was also studied. The reaction rate constants, k, were determined to be 0. 018 3, 0. 020 7, 0. 024 1, 0. 027 0, 0. 028 8, 0. 031 9 at 40,50,60,70,80 and 90 ℃, respectively. The correlation between the reaction rate constant k and temperature T was Ink=-1 267.1 × （1/T）＋0. 055（r^2 =0. 990 2）. The reaction activation energy, E,, was found to be 10.53 kJ · mol^-1 , much lower than the activation energy of general chemical reactions （typically 20-150 kJ · mol^-1 ）, which was consistent with the observation that the preparation of ^99Tc^m-BIPrDP took place rapidly. In addition, based on the data of the radiolabeling yield （RLY） at different temperatures, a correlation between the RLY and temperature was developed as ln[RLY/（1-RLY）]=-6 218.4/T＋ 19.84. This correlation suggests that, in order to achieve radiolabeling yields of higher than 90%, the reaction temperature should be higher than 79.31 ℃.

关 键 词：99Tcm-BIPrDP 骨显像剂 反应动力学 

分 类 号：R817[医药卫生—影像医学与核医学]