Zou J, Gao T, Wang Y, Ren M, Liu D, Long R, Cheng Y, Liu M, Xu Z, Xie Z, Lv P, Yuan L, Han H
Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China.
Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2025 Jun 18;57(3):562-568. doi: 10.19723/j.issn.1671-167X.2025.03.021.
To explore the distribution and clearance of Tc labeled diethylenetriamine pentaacetic acid (Tc-DTPA) in different brain regions of adult rats after administration through brain extracellular space (ECS) pathway.
After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq (100 μCi) of Tc-DTPA into the caudate nucleus and thalamus of SD rats through stereotactic positioning of rat brain, the single photon emission computed tomography/computed tomography (SPECT/CT) for small animals was used for imaging at different time points, and the dyna-mic distribution and clearance of the tracer in the whole body were observed continuously. The SD rats were injected with Tc-DTPA into thalamus and caudate nucleus respectively for biological distribution . They were put to death 4 h later. Their blood and urine were collected. The brain, cerebellum, heart, liver, spleen, lung, and kidney were taken and weighed by γ counter to measure its radioactivity.
SPECT/CT imaging results showed that after Tc-DTPA was administered through brain ECS, the radioactivity was concentrated in the brain, kidney and bladder. The tracer administered to the left caudate nucleus was preferentially drained to the right cerebellum, while the tracer administered to the right caudate nucleus was preferentially drained to the left cerebellum. There was a phenomenon of "contralateral cerebellar dominant drainage" in the caudate nucleus. The thalamic area preferentially drained to the ipsilateral cerebellum after administration. Four hours after administration via ECS, high radioactive uptake appeared in urine, cerebellum and brain, followed by blood and kidney. The radioactive uptake values of heart, liver, spleen and lung were low, which were mainly excreted through urinary system.
Intracerebral ECS administration is a promising method of administration, but there are significant differences in distribution and clearance in different brain regions. This study further expands the content and significance of "ECS regions", and also provides an important theoretical foundation for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.
探讨经脑细胞外间隙（ECS）途径给药后，锝标记的二乙三胺五乙酸（Tc-DTPA）在成年大鼠不同脑区的分布及清除情况。
通过大鼠脑立体定位，将体积为2 μL、放射性活度约为3.7 MBq（100 μCi）的Tc-DTPA注入SD大鼠的尾状核和丘脑，在不同时间点利用小动物单光子发射计算机断层扫描/计算机断层扫描（SPECT/CT）进行成像，连续观察示踪剂在全身的动态分布及清除情况。将SD大鼠分别注入丘脑和尾状核的Tc-DTPA进行生物分布研究。4 h后处死大鼠，收集血液和尿液。取脑、小脑、心脏、肝脏、脾脏、肺和肾脏，用γ计数器称重并测量其放射性。
SPECT/CT成像结果显示，经脑ECS途径给予Tc-DTPA后，放射性集中在脑、肾和膀胱。注入左侧尾状核的示踪剂优先引流至右侧小脑，而注入右侧尾状核的示踪剂优先引流至左侧小脑。尾状核存在“对侧小脑优势引流”现象。给药后丘脑区域优先引流至同侧小脑。经ECS给药4 h后，尿液、小脑和脑出现高放射性摄取，其次是血液和肾脏。心脏、肝脏、脾脏和肺的放射性摄取值较低，主要通过泌尿系统排泄。
脑内ECS给药是一种有前景的给药方式，但不同脑区的分布和清除存在显著差异。本研究进一步拓展了“ECS区域”的内涵和意义，也为未来通过脑ECS治疗脑病和研发新药提供了重要的理论基础。
