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Beakc Research of Molecular Imaging on Familial Amyloiclotic Ployneuropathy

Beakc 家族性淀粉样变性多发性神经病的分子影像研究

基本信息

批准号：
17591281
负责人：
TOMIYOSHI Katsumi
金额：
$ 2.5万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

项目摘要

Abstract of Research ProjectsOBJECTS: Alzheimer's disease (AD)has been the main diseases among the elderly. The disease is neurophathologically characterized by the formation of Amiloid β plaques (A,β plaques) that is consist of primarily of filaments of hypexphasphorylated tau protein. This project is aimed at labeling 1 brome 2,5 -bis (3-hydraxycarbony1-4-hydroxy)styrylbenzene (BSB)that has a high affinity for the Amiloid β plaques. we have implemented the methods. and labeled by using radio isotopes such as I -125, I-123 for Single Photon. Emission Thmography (SPECT)or F-18, C-11 positron nuclides for PETMETHODS: 1-bromo 2,5 -bis (3-hydroxycarbony1-4-hydroxy) styrylbenzene (BSB)was obtained from the Dojindo laboratories which are collaborated with our research projects. Experiments on SPECT for labeling radio isotopes On I-125 were taken place at Kumamoto University Institute of Resource Development and Analysis (IRDA).1)Radio Isotope exchange methods : One mg of BSB was dissolved. … More in 2 ml acetonitrile(AcCN)with a small portion of Di Methyl Sulfoxide(DMSO). Added Na 1251(1MBq)to the solvent and heated up to several temperature(22℃, 90℃ and 120℃)for several times (10,30,60min) in reflux distilled reactor2)HPLC analysis : Column : Portrsil-10SAX(4.6x 250mm) Whatman, Moble Phase : 10mMNaH2PO4, Flow rate : 2ml /min and UV absorbed λ : 280nm.Final results are shown in Fig. 1 that is BSB peak UV peak, in Fig2 that is a small peak shown labeled I-125 BSB at the condition of 90℃ and 30 minute reaction time, in Fig. 3 that is shown a bigger peak of I-125 BSB at the condition of 120℃ 60 minutes.Explanations in Figures : Retention time for BSB are about from 7 to 8 minutes in lower spectrum on UV detector and the corresponding peak of I-125 labeled BSB is about from 7 to 8 minutes at upper spectrum on Radiodetector.3)Another experiments on PET for labeling radio isotopes on F-18 were taken place at Japanese Red Cross Kumamoto Health Care Center where positron nuclides are able to provide and has experiments system was provided.18F ion was trapped in QMA and dissolved in K2CO3solution. BSB was dissolved in 1ml of AcCN with a small portion of DMSO. 18F ion in K2CO3 and Kriptfix 222 was brought to the reactor and heated up 90℃ to get removed of liquids. BSB solution was reacted with 18F-Kriptfix 222 complex at 90℃ again for 15 minutes. HPLC analysis conditions of flow rate 1ml/ min was only different from SPRCT. Final results experiments are shown: in Fig. 4 that is SBS peak at about 4 minutes and in Fig. 5 that is a broad. peak _shown no labeled BSB on a condition of 90℃ and 15 minute reaction time, in Fig.6 that is shown a peak of F-18/labeled some other than BSB on the condition of 90℃ and 15 minutes with a catalysis of FeCl3.Explanations in Figures : Retention time for BSB are about from4 to 4.5 minutes in lower spectrum on UN detector and the corresponding peak of F-18 labeled BSB were not found on from 4 to 5 minutes at upper spectrum on Radiodetector.Results: I-125 labeled BSB was obtained by described methods and radiochemical yield was less than 10%. Experiments are more needed for high radiochemical yield. F-18 labeled BSB was no found. Further Experiments are to be followed Less

研究项目摘要目的：阿尔茨海默病(AD)一直是老年人的主要疾病。这种疾病的神经学特征是形成Amilidβ斑块(A，β斑块)，主要由低磷脂酰化的tau蛋白细丝组成。本项目旨在标记对淀粉样蛋白β斑块具有高亲和力的1-溴-2，5-双(3-羟基碳基-1-4-羟基)苯并苯。我们已经实现了这些方法。并通过使用放射性同位素标记，例如用于单光子的I-125、I-123。方法：1-溴-2，5-双(3-羟基碳基-1-羟基)苯基苯(BSB)来自与我们的研究项目合作的Dojindo实验室。放射性同位素标记实验是在熊本大学资源开发与分析研究所(IrDA)进行的。1)放射性同位素交换方法：溶解1 mg BSB。…更多的是在2毫升乙腈(AcCN)中加入一小部分二甲基亚砜(DMSO)。在溶剂中加入Na1251(1MBq)，在回流蒸馏反应器中加热到几个温度(22℃，90℃和120℃)几次(10，30，60min)2)高效液相分析：色谱柱：Portrsil-10SAX(4.6×250 mm)Whatman，流动相：10mMNaH_2PO_4，流速：2ml/m in，紫外光吸收λ：280 nm。图1是BSB峰UV峰，图2是在90℃，30分钟反应时间下标记为I-125 BSB的小峰，如图3所示，在120℃60min的条件下，I-125BSb的峰较大。如图所示：BSb在紫外光探测器上的保留时间约为7~8分钟，而I-125标记的BSB在无线电探测器上的相应峰约为7~8分钟。3)在日本红十字会熊本保健中心进行了正电子核素标记F-18放射性同位素的另一实验，该中心提供了正电子核素提供的实验系统。BSB溶于1ml AcCN和一小部分DMSO中。将K2CO3和Kritfix 222中的18F离子带入反应堆，加热90℃以去除液体。BSB溶液与18F-Krigtfix 222络合物在90℃下反应15分钟。流速为1ml/min的高效液相色谱分析条件仅与SPRCT有所不同。最后的实验结果显示：在图4中，这是SBS峰值在大约4分钟，而在图5中，这是一个很宽的。当反应时间为15分钟，反应时间为90℃时，峰位未见标记的BSB，如图6所示，在90℃的条件下，FeCl3催化反应15分钟，出现一个F-18标记的标记BSB的峰。图中解释：在UN探测器的下谱中，标记的BSB的保留时间为4~4.5min，而在探测器的上光谱中，4~5分钟未发现相应的标记的BSB。要想获得高的放射化学产额，更需要实验。未发现F-18标记的BSB。进一步的实验将被更少地跟踪