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"con-tralateral 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 radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.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 ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.

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"con-tralateral 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 radioac-tive uptake appeared in urine,cerebellum and brain,followed by blood and kidney.The radioactive up-take values of heart,liver,spleen and lung were low,which were mainly excreted through urinary sys-tem.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 ex-pands the content and significance of"ECS regions",and also provides an important theoretical founda-tion for the treatment of encephalopathy and the research of new drugs through brain ECS in the future.