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題 名 | SPECT Imaging Agents for Dopamine and Serotonin Transporters in the Brain=腦部多巴胺轉運體及血清素轉運體單光子放射電腦斷層掃描造影劑 |
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作 者 | 孔繁淵; 魏孝萍; 孔美萍; | 書刊名 | 核子醫學雜誌 |
卷 期 | 13:3 2000.09[民89.09] |
頁 次 | 頁165-174 |
分類號 | 418.346 |
關鍵詞 | 單光子放射電腦斷層掃描; 多巴胺轉運體造影劑; 血清素轉運體造影劑; SPECT DAT imaging agents; SRET imaging agents; |
語 文 | 英文(English) |
中文摘要 | 應用正子放射電腦斷層掃描(PET)或單光子放射電腦斷層掃描(SPECT)進行腦神經受體體內造影為研究中樞神經系正常或病理狀態的有利工具。眾所週知PET在解析度、靈敏度及定量能力方面優於SPECT,但由於配置SPECT的醫院比較普遍,因此例行的核醫檢查仍以SPECT為主。多巴胺轉運體(dopamine transporter, DAT)結合劑可用於體內或體外評估節DAT的變異,尤其針對腦基底核及黑體質多巴胺神經細胞選擇性退化的巴金森氏症(Parkinson's disease, PD)。廷牛來以碳-11-CFT、碘-123-β-CIT、碘-123--β-CIT、碘-123-IPT及碘-123-altropane進行的研究發現這些DAT造影劑在putamen區域分佈的減少與PD臨床症狀有顯著的相關性。這些成果啟示DAT造影劑可進而發展為PD病人診斷及治療追蹤的利器。由於加速器生產的碘-123價格百倍於鎝-99m,加上鎝-99m容易獲得與標幟藥物的方便使用優勢,都提供發展鎝-99m藥物的良好契機。鎝-99m-TRODAT-1為成功開發的DAT造影劑,其研發過程引入一雙氮雙硫(N2S2)小分子與鎝形成[TcvO]+3 N2S2電中性基團,以大幅提昇靜脈注射後將標幟藥物帶入腦組織之機率。鎝-99m-TRODAT-1已被證實可有效用於偵測PD病人DAT的耗損。血清素轉運體(serotonin transporters, SERT)在調節血清素神經系統功能方面扮演重要角色。用於PET或SPECT造影的SERT選擇性結合藥物將有利於以非侵襲性方法研究人腦SERT功能。碳-11-(+)McN5652為迄今最具潛力的SERT/PET造影藥物,具備優異的血清素(5-HT)回收抑制能力(Ki=0.40 nM)。碳-11-(+)McN5652的PET造影研究顯示與已知人腦SERT密度相關性良好。在SERT/SPECT新造影藥物方面,最近發展出的碘標幟IDAM及ADAM都題biphenylthio衍生物。體外結合試驗結果顯示IDAM及ADAM均顯現對SERT具備極佳的親和力與選擇性(Kd分別為0.1及0.2nM)。以碘-123-IDAM或碘-123-ADAM對狒狒進行的SPECT造影結果均顯示在富含SERT的中腦區域有極佳的分佈。 |
英文摘要 | In vivo imaging of receptors in the brain using PET (positron emission tomography) or SPECT (single photon emission computed tomography)provides powerful tools for functional study of central nervous system (CNS) in normal or disease states. It is well recognized that PET has higher resolution, higher sensitivity and better quantitative capability than SPECT, however, there are more hospitals equipped with SPECT scanners; therefore, SPECT is more practical as a routine procedure. Ligands for dopamine transporters (DAT) are useful in evaluating changes in presybnaptic DAT sites in vivo and in vitro, especially in patients with Parkinson's disease (PD), which is characterized by a selective loss of dopamine neurons in the basal ganglia and substantia nigra. Recent publications using [11C]CFT, [123] β-CIT, [123l]-FP-β-CIT, [123l]lPT and [123l]altropane suggest a strong correlation between the decrease in localization in the putamen area and PD symptoms. The results provide an impetus for further development of these agents for diagnosing and monitoring the treatment of PD patients. Since 123l is a cyclotron produced isotope, which costs 100 times more than a similar 99mTc labeled agent and the advantage of ready availability and ease of use with 99mTc agents provide a strong incentive for their development. A successful 99mTc labeled DAT imaging agent, [99mTc]TRODAT-1, was developed. In developing [99mTc]TRODAT-1, a small and neutral [TcvO]+3 N2S2 core was employed to maximize the possibility of initial delivery of radioactive tracers into the brain following an intravenous injection. [99mTc]TRODAT-1 has been shown to be a useful imaging agent for monitoring DAT loss in Parkinson's patients. Serotonin transporters (SERT) play an important role in modulating the serotonergic neuronal function. Selective tracers of SERT for PET and SPECT may be important to study this specific binding sites non-invasively in the human brain. The most promising radioligand of SERT described to date is [99mTc C](+)McN5652 for PET imaging. It showed an excellent inhibition on 5-HT reuptake (Ki=0.40 nM). Specific binding of [11C](+)McN5652 by PET imaging correlates well with the known density of SERT in the human brain. Recently, novel iodinated ligands, IDSM and ADAM, based on biphenylthio derivatives were developed. In vitro binding study showed that IDAM and ADAM displayed an excellent affinity and selectivity to SERT sites (Kd=0.1 and 0.2nM, respectively). SPECT imaging using [123l]lDAM or [123l]ADAM in baboons demonstrated an excellent localization in regions of the midbrain area known to have a high concentration of SERT binding sites. |
本系統中英文摘要資訊取自各篇刊載內容。