Quantification of 4-[18F]-ADAM and 99mTc-ECD in the Brain of Conscious and Anesthetized Mice Using High Resolution Single-photon Emission and Positron Emission Tomography

• Main Authors: DAVID, TAT-WEI TAN, 陳金財
• Other Authors: Jyh-Cheng Chen
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/57582801949557993682

碩士 === 國立陽明大學 === 生物醫學影像暨放射科學系 === 101 === 英文摘要 Objective: In vivo small animal imaging, such as SPECT or PET, in contrast to human imaging, requires restriction of head and body movements and used anesthetic agents in studies during experiments. The anesthesia used in animal imaging will affect neural metabolic and physiologic neural functions. These effects are difficult to access in animal PET/SPECT studies, thus design an appropriate method for awake animal imaging is important. The aim of this study was to establish a simple awake in vivo imaging device and application of awake animal PET/SPECT/CT imaging in mice were performed in awake and freely moving state and the influence of isoflurane and pentobarbital anesthesia on brain region of interest, which was evaluated using 99mTc-ECD and 4-[18F]-ADAM. Methods: To perform the PET/SPECT study in awake mice, we first developed a simple head and body holder to enable brain PET/SPECT imaging of awake mice. Before the scanning, each mouse was trained twice a day for five days to acclimate to the scanning atmosphere for 1 hour. Mice were injected via tail vein with the brain perfusion and serotonin transporter radiotracer 99mTc-ECD and 4-[18F]-ADAM, then placed in a scanner for brain dynamic and static imaging. Finally, Semi-quantitative of static data of 99mTc-ECD was performed for brain regional index (BRI) and we used image derived binding potential (BP) for 4-[18F]-ADAM analysis. The quantitative kinetic of 99mTc-ECD was performed for one compartment model and quantitative kinetic of 4-[18F]-ADAM was perform for binding potential based on simplified reference tissue model (SRTM) with an reference tissue of cerebellum under both awake and anaesthetized conditions. Results: Regions of interest were drawn in the 99mTc-ECD dynamic and static images of the brain region of striatum, cortex, hippocampus, thalamus, cerebellum, hypothalamus and midbrain for analysis. Calculation of BRI revealed higher value in the hippocampus, thalamus, and the midbrain in the isoflurane anesthesia and higher value in the thalamus, cerebellum, and the midbrain in the pentobarbital anesthesia, compared with awake state. Freely moving state only showed difference in cerebellum compared with awake. The key calculated kinetic parameters, which are volume of distribution of compartment and the rate of tracer leaving the compartment, also revealed significantly higher values in isoflurane and pentobarbital anesthesia. Semi-quantitative of 4-[18F]-ADAM analyses revealed that isoflurane and pentobarbital anesthesia and freely moving significantly increased BP in midbrain (56 % and 41 % and 50 %), striatum (39 % and 26 % and 43 %), and thalamus (54 % and 42 % and 54 %), respectively. The results of kinetic analyses of SRTM show that isoflurane and pentobarbital anesthesia increased binding potential of nondisplaceable uptake (BPnd) in midbrain by 53 %, and 44 %, respectively, compared to that in awake state. Conclusion: To our knowledge, this is the first study to report quantitative kinetic analysis of 99mTc-ECD and 4-[18F]-ADAM in mice that have been awake throughout SPECT and PET imaging. This study demonstrated that anesthesia can have a substantial effect on brain perfusion and serotonin transporter tracer studies. The awake animal SPECT and PET device is useful for research into in vivo functional brain molecular imaging for investigating distinct tracer pharmacokinetics in awake animals.