A technetium-99m SPECT imaging agent which targets the dopamine transporter in primate brain

被引:59
作者
Meltzer, PC
Blundell, P
Jones, AG
Mahmood, A
Garada, B
Zimmerman, RE
Davison, A
Holman, BL
Madras, BK
机构
[1] NEW ENGLAND REG PRIMATE RES CTR, SOUTHBOROUGH, MA 01772 USA
[2] HARVARD UNIV, SCH MED, DEPT PSYCHIAT, SOUTHBOROUGH, MA 01772 USA
[3] HARVARD UNIV, BRIGHAM & WOMENS HOSP, SCH MED, BOSTON, MA 02115 USA
[4] MIT, CAMBRIDGE, MA 02139 USA
关键词
D O I
10.1021/jm960868t
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first Tc-99m-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide Tc-99m across the blood-brain barrier in sufficient quantity to obtain in. vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated Tc-99m agents which can label specific transporter and receptor targets in the central nervous system.
引用
收藏
页码:1835 / 1844
页数:10
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