Objective: To explore the distribution and clearance of 99mTc labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) in different brain regions of adult rats after administration through brain extracellular space (ECS) pathway.
Methods: After the injection of a volume of 2 μL and radioactive activity of about 3.7 MBq (100 μCi) of 99mTc-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 99mTc-DTPA into thalamus and caudate nucleus respectively for biological distribution in vivo. 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.
Results: SPECT/CT imaging results showed that after 99mTc-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.
Conclusion: 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.
目的: 探索 99mTc-二乙基三胺五乙酸(99mTc-DTPA)经脑细胞外间隙(extracellular space, ECS)途径在不同脑区给药后，正常成年大鼠脑内及全身的药物动态分布及消除规律。
方法: 使用鼠脑立体定位仪将SD大鼠固定，将体积为2 μL、放射性活度为3.7 MBq (100 μCi) 的 99mTc-DTPA分别注入大鼠的尾状核区和丘脑区，使用小动物单光子发射型计算机断层扫描/计算机断层扫描(single photon emission computed tomography/computed tomography, SPECT/CT)在不同时间显像，连续观察示踪剂的动态分布和消除规律。生物体内分布实验是在大鼠丘脑区和尾状核区注入 99mTc-DTPA，4 h后处死大鼠，收集血液、尿液，取大脑、小脑、心、肝、脾、肺、肾，称重后用γ计数器测定其放射性强度。
结果: 99mTc-DTPA经脑ECS途径给药后，放射性分布浓聚于脑、肾和膀胱，左侧尾状核区给药的示踪剂优先向右侧小脑引流，右侧尾状核区给药的示踪剂优先向左侧小脑引流，尾状核区给药存在“对侧小脑优势引流”现象，而丘脑区给药后会优先向同侧小脑引流。给药4 h后，尿液、小脑和大脑出现高放射性摄取，其次是血液和肾，心、肝、脾、肺的放射性摄取值均较低，主要经泌尿系统排泄。
结论: 经脑ECS途径给药是一种极具前景的给药方法，但不同脑区经该途径给药后的动态分布与消除规律存在明显差异，本研究进一步拓展了“脑分区”的内容与意义，也为未来经脑ECS途径给药进行脑病治疗和新药研发提供了理论基础。
Keywords: 99mTc-DTPA; Brain; Extracellular space; Interstitial fluid; Tissue distribution.