Beakc Research of Molecular Imaging on Familial Amyloiclotic Ployneuropathy

研究项目摘要阿尔茨海默病（Alzheimer's disease，AD）已成为老年人的主要疾病.该疾病的神经病理学特征是形成主要由高磷酸化tau蛋白细丝组成的Amiloid β斑块（A，β斑块）。本项目旨在标记对Amiloid β斑块具有高亲和力的1雀麦2，5-双（3-羟基羰基1 -4-羟基）苯乙烯基苯（BSB）。我们已经实施了这些方法。并通过使用放射性同位素如I-125、I-123进行单光子标记。方法：从与我们的研究项目合作的Dojindo实验室获得1-溴-2，5-双（3-羟基羰基-4-羟基）苯乙烯基苯（BSB）。在熊本大学资源开发和分析研究所（IRDA）进行了用于标记放射性同位素On-125的SPECT实验。1）放射性同位素交换方法：溶解1 mg BSB。 关于我们 在2 ml乙腈（AcCN）中，加入少量二甲基亚砜（DMSO）。向溶剂中加入Na 1251（1 MBq）并加热至几个温度（22℃、90℃和120℃）多次2）HPLC分析：柱：Portrsil-10 SAX（4.6x 250 mm）Whatman，流动相：10 mM NaH 2 PO 4，流速：2 ml/min，UV吸收λ：最终结果显示在图1中，即BSB峰UV峰，在图2中，即在90℃和30分钟反应时间的条件下显示的标记为I-125 BSB的小峰，在图3中显示了在120℃ 60分钟条件下I-125 BSB的较大峰。在紫外检测器上，BSB的保留时间在较低的光谱中约为7 - 8分钟，125标记的BSB在放射性探测器上的上光谱约为7 - 8分钟。3）在PET上标记放射性同位素F-的另一个实验18例在日本红十字会熊本保健中心进行，该中心能够提供正电子核素并提供了实验系统。18 F离子被捕获在QMA中，溶解于K2 CO 3溶液中。将BSB溶于含有少量DMSO的1 ml AcCN中。将K2 CO 3和Kriptfix 222中的18F离子引入反应器并加热至90℃以除去液体。BSB溶液与18F-Kriptfix 222复合物在90℃下再次反应15分钟。HPLC分析条件仅为流速1 ml/ min，与SPRCT不同。实验的最终结果如下所示：图4中为约4分钟处的SBS峰，图5中为宽峰。峰_在90℃和15分钟反应时间的条件下未显示标记的BSB，在图6中，在90℃和15分钟的条件下，在FeCl 3的催化下，显示了F-18/标记的一些非BSB的峰。在UN检测器上，BSB的保留时间约为4 - 4.5分钟，在低光谱中，相应的F-峰结果：用上述方法制备的125 I标记BSB，放化产率小于10%。高放化产额需要更多的实验。没有发现F-18标记的BSB。进一步的实验有待进行。

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