Efange S M, Kung H F, Billings J J, Blau M
Department of Nuclear Medicine, State University of New York, Buffalo 14215.
J Med Chem. 1988 May;31(5):1043-7. doi: 10.1021/jm00400a028.
In developing clinically useful 99mTc-labeled radiopharmaceuticals for the evaluation of regional cerebral perfusion with single photon emission computed tomography (SPECT), a number of substituted alkyl(aryl)piperidinyl bis(aminoethanethiol) ligands for chelating [99mTc]TcO(III) were synthesized. Each ligand forms two diastereomers, syn and anti, after reacting with a racemic mixture of the ligand. The diastereomers were separated by high-pressure liquid chromatography. In biodistribution studies conducted in rats, the diastereomers exhibit widely disparate brain uptake values; however, this disparity seems to diminish as the steric bulk of the substituent at the C-4 position of the piperidinyl moiety increases. Furthermore, all the complexes evaluated failed to show a prolonged retention in the rat brain, suggesting that further structural modification may be necessary to obtain clinically useful complexes from this class of compounds.
在开发用于通过单光子发射计算机断层扫描（SPECT）评估局部脑灌注的具有临床实用性的99mTc标记放射性药物时，合成了多种用于螯合[99mTc]TcO(III)的取代烷基（芳基）哌啶基双（氨基乙硫醇）配体。每个配体与该配体的外消旋混合物反应后会形成两种非对映异构体，即顺式和反式。通过高压液相色谱法分离这些非对映异构体。在对大鼠进行的生物分布研究中，这些非对映异构体表现出相差很大的脑摄取值；然而，随着哌啶基部分C-4位取代基的空间位阻增大，这种差异似乎会减小。此外，所评估的所有配合物在大鼠脑中均未显示出长时间的滞留，这表明可能需要进一步进行结构修饰才能从这类化合物中获得具有临床实用性的配合物。
