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Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (3): 562-568. doi: 10.19723/j.issn.1671-167X.2025.03.021

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Dynamic distribution and clearance of 99mTc-DTPA in brain extracellular space

Jing ZOU1,2,3, Tianzi GAO1,3, Yang WANG1,3, Mengmeng REN1,2,3, Dongyang LIU4, Ren LONG1,2,3, Yumeng CHENG1,3,5, Meng LIU6, Zhengren XU7, Zhaoheng XIE1,3, Pengyu LV8, Lan YUAN1,2,3,*(), Hongbin HAN1,3,5,*()   

  1. 1. Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
    2. Department of Chemical Biology, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
    3. Beijing Key Lab of Magnetic Resonance Imaging Device and Technique, Beijing 100191, China
    4. Peking University Third Hospital Drug Clinical Trial Institute, Beijing 100191, China
    5. Department of Radiology, Peking University Third Hospital, Beijing 100191, China
    6. Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China
    7. Department of Natural Medicines, Peking University School of Pharmaceutical Sciences, Beijing 100191, China
    8. Department of Mechanics and Engineering Science, Peking University School of Engineering, Beijing 100871, China
  • Received:2022-05-10 Online:2025-06-18 Published:2025-06-13
  • Contact: Lan YUAN, Hongbin HAN
  • Supported by:
    the National Major Scientific Research Instrument Development Project(61827808); the National Natural Science Mathematics Tianyuan Foundation(12126601); the Beijing Natural Science Foundation(Z210007)

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Abstract:

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.

Key words: 99mTc-DTPA, Brain, Extracellular space, Interstitial fluid, Tissue distribution

CLC Number: 

  • R817.4

Figure 1

SPECT/CT images of 99mTc-DTPA injected into the left caudate nucleus of normal SD rats A and C, original drawings; B and D, enlarged view of signal. P, horizontal axis; L, left sagittal; SPECT/CT, single photon emission computed tomography/computed tomography."

Figure 2

SPECT/CT images of 99mTc-DTPA injected into the right caudate nucleus of normal SD rats A and C, original drawings; B and D, enlarged view of signal. P, horizontal axis; R, right sagittal; SPECT/CT, single photon emission computed tomography/computed tomography."

Figure 3

SPECT/CT images of 99mTc-DTPA injected into the left thalamus of normal SD rats A and C, original drawings; B and D, enlarged view of signal. P, horizontal axis; L, left sagittal; SPECT/CT, single photon emission computed tomography/computed tomography."

Figure 4

SPECT/CT images of 99mTc-DTPA injected into the right thalamus of normal SD rats A and C, original drawings; B and D, enlarged view of signal. P, horizontal axis; R, right sagittal; SPECT/CT, single photon emission computed tomography/computed tomography."

Table 1

In vivo distribution of 99mTc-DTPA 4 h after injection into the right caudate nucleus and the right thalamus of normal SD rats (n=5)"

Organs and tissues Radioactive uptake value/(%ID/g), $\bar x \pm s$
R-Cn R-Tha
Olfactory bulb 45.66±13.48 31.73±6.45
Cerebellum 26.06±16.26 73.70±25.17
Brain-R 159.85±85.37 221.93±54.04
Brain-L 28.60±13.56 49.73±16.64
Heart 0.44±0.30 1.20±0.52
Liver 0.68±0.68 0.87±0.39
Spleen 0.21±0.08 0.87±0.47
Lung-R 0.84±0.40 2.42±0.94
Lung-L 0.60±0.34 2.15±0.87
Kidney-R 2.98±1.55 5.30±1.50
Kidney-L 2.74±1.25 5.61±1.56
Blood 2.49±0.88 4.83±1.83
Urine 102.32±25.61 312.55±48.10
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