Neuroimaging in various animal models using single photon emission computed tomography and positron emission tomography

Autor: I-Hsun Li, 李宜勳
Rok vydání: 2009
Druh dokumentu: 學位論文 ; thesis
Popis: 98
Parkinson’s disease (PD) affects both dopaminergic and serotonergic systems. In this study, we simultaneously evaluated dopamine and serotonin transporters in primates using dual isotope SPECT imaging and compared the results with traditional single isotope imaging. Four healthy and one 6-OHDA induced PD monkeys were used for this study. SPECT was performed over 4 h after individual or simultaneous injection of [99mTc]-TRODAT-1 (a dopamine transporter imaging agent) and [123I]-ADAM (a serotonin transporter imaging agent). The results showed that the image quality and uptake ratios in different brain regions were comparable between single and dual isotope studies. The striatal [99mTc]-TRODAT-1 uptake in the PD monkey was markedly lower than that in normal monkeys. The uptake of [123I]-ADAM in the midbrain of the PD monkey was comparable to that in the normal monkeys, but there were decreased uptakes in the thalamus and striatum of the PD monkey. Our results suggest that dual isotope SPECT using [99mTc]-TRODAT-1 and [123I]-ADAM can simultaneously evaluate changes of dopaminergic and serotonergic systems in a PD model. 3, 4-Methylenedioxymethamphetamine (MDMA, “ecstasy”) has toxic effects on serotonergic neurons in the brain. The second study was to determine whether N,N-dimethyl-2-(2-amino-4-[18F]-fluorophenylthio) benzylamine (4-[18F]-ADAM; a serotonin transporter imaging agent) and micropositron emission tomography (micro-PET) can be used to examine in vivo the effect of fluoxetine on MDMA-induced loss of serotonin transporters in rat brain. Male Sprague-Dawley rats were injected with fluoxetine (1 dose, 5 mg/kg, subcutaneously [s.c.]) followed by MDMA (twice a day for 4 consecutive days, 10 mg/kg, s.c.). Micro-PET with 4-[18F]-ADAM was performed on days 4, 10, 17, 24, and 31. In addition, the time course of occupancy by fluoxetine at 4-[18F]-ADAM sites was measured. Specific 4-[18F]-ADAM uptake ratios (SURs) were calculated from the micro-PET imaging data for various brain regions. Immunohistochemistry was performed 7 days after the last micro-PET scan. From day 4 to day 31, SURs were markedly decreased (by approximately 55%-75% compared to control values) in all brain regions in MDMA-treated rats. The effect of MDMA was markedly attenuated (approximately 30%-50%) by fluoxetine. The fluoxetine-induced decrease in uptake in different brain regions was 40% to 75% at 90 min postinjection, and this decrease returned to baseline values in most brain regions by day 31. The distribution and intensity of serotonin transporter (SERT) immunostaining in the brain paralleled the PET imaging results, suggesting that a single dose of fluoxetine provides long-lasting protection against MDMA-induced loss of SERT and that such neuroprotection is detectable in vivo by 4-[18F]-ADAM micro-PET.
Databáze: Networked Digital Library of Theses & Dissertations
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