本文選題：造影劑 + MRI　； 參考：《中國科學(xué)院研究生院(武漢物理與數(shù)學(xué)研究所)》2014年碩士論文

【摘要】：高密度脂蛋白(HDL)是一種血管中普遍存在的脂質(zhì)-蛋白復(fù)合納米粒子,其主要作用是將血管壁中和周圍器官中的膽固醇等脂質(zhì)運(yùn)輸回肝臟,對巨噬細(xì)胞上豐富表達(dá)的SR-BI受體具有特異性。動(dòng)脈粥樣硬化是一種嚴(yán)重影響人類健康的疾病,是引起心血管疾病的主要原因,而心血管疾病已成為發(fā)達(dá)國家最主要的死因。一般認(rèn)為動(dòng)脈粥樣硬化與巨噬細(xì)胞進(jìn)入動(dòng)脈血管壁形成泡沫狀細(xì)胞有關(guān)。因此,實(shí)現(xiàn)對巨噬細(xì)胞的高靈敏檢測,對于動(dòng)脈粥樣硬化形成過程的研究具有十分重要的意義。近年來,人們利用重組HDL (rHDL)顆粒作為載體,發(fā)展了MRI, CT和熒光等一系列造影劑,用于巨噬細(xì)胞和動(dòng)脈粥樣硬化斑塊的檢測。順磁化學(xué)交換飽和轉(zhuǎn)移(PARACEST)是新近發(fā)展起來的一種磁共振方法。不同于傳統(tǒng)的磁共振成像方法,PARACEST主要依靠鑭系金屬中心上結(jié)合水與自由水之間的化學(xué)交換。當(dāng)對結(jié)合水施加飽和脈沖照射時(shí),由于化學(xué)交換的存在,自由水的磁共振信號發(fā)生變化,通過檢測自由水信號的變化,實(shí)現(xiàn)CEST造影劑的間接檢測。相比于傳統(tǒng)MRI造影劑,PARACEST造影劑具有對周圍環(huán)境敏感的特點(diǎn)。但是,PARACEST造影劑具有較低的靈敏度,而發(fā)展受到限制。關(guān)于提高PARACEST造影劑的靈敏度,主要有兩個(gè)思路,一種是將多個(gè)PARACEST探針連接大分子量分子上,另一種是將小分子探針負(fù)載在納米載體上�；谝陨媳尘�,我們設(shè)計(jì)并制備了一種高靈敏PARACEST MR/熒光雙模態(tài)造影劑,Eu-Rhod-rHDL,實(shí)現(xiàn)了對PARACEST方法靈敏度的提高。發(fā)展雙模態(tài)造影劑的優(yōu)點(diǎn)在于其可以實(shí)現(xiàn)PARACEST和熒光兩種成像手段的互補(bǔ)。為了使rHDL造影劑能夠具有CEST效果,我們首先合成了一種含有Eu(Ⅲ)基團(tuán)的磷脂,具有PARACEST的效應(yīng)。通過多種磷脂和載脂蛋白的自組裝,制得了rHDL雙模態(tài)造影劑。而后對造影劑進(jìn)行了多種表征以及CEST性質(zhì)的測定。相比傳統(tǒng)小分子PARACEST造影劑,Eu-Rhod-rHDL的靈敏度提高了129倍,從而擴(kuò)展了PARACEST的應(yīng)用范圍,有利于今后對低濃度物質(zhì)的檢測。同時(shí),通過細(xì)胞實(shí)驗(yàn)發(fā)現(xiàn)Eu-Rhod-rHDL對巨噬細(xì)胞具有特異性,可以選擇性進(jìn)入巨噬細(xì)胞,從而可以實(shí)現(xiàn)對巨噬細(xì)胞的檢測。這種雙模態(tài)rHDL還有潛力發(fā)展對動(dòng)脈粥樣硬化的PARACEST檢測。
[Abstract]:High density lipoprotein (HDL) is a kind of lipide-protein composite nanoparticles widely used in blood vessels. The main function of HDL is to transport cholesterol and other lipids from the walls and surrounding organs of blood vessels back to the liver. It is specific to SR-BI receptors which are expressed on macrophages. Atherosclerosis is a serious disease affecting human health, and is the main cause of cardiovascular disease, which has become the most important cause of death in developed countries. Atherosclerosis is thought to be associated with macrophages entering the arterial wall to form foam cells. Therefore, the highly sensitive detection of macrophages is of great significance for the study of atherosclerosis. In recent years, a series of contrast agents, such as MRI, CT and fluorescence, have been developed using recombinant HDL (rHDL) particles as carriers for the detection of macrophages and atherosclerotic plaques. Paramagnetism exchange saturation transfer (PARACEST) is a newly developed magnetic resonance technique. Unlike the traditional magnetic resonance imaging method, PARACEST mainly depends on the chemical exchange between the bound water and free water on the lanthanide metal center. In the presence of chemical exchange, the magnetic resonance signal of free water changes when the combined water is irradiated with saturated pulse. The indirect detection of CEST contrast agent is realized by detecting the change of free water signal. Compared with conventional MRI contrast agent, PARACEST contrast agent is sensitive to the surrounding environment. However, PARACEST contrast agent has low sensitivity, and its development is limited. There are two main ways to improve the sensitivity of PARACEST contrast agent, one is to attach multiple PARACEST probes to large molecular weight molecules, the other is to load small molecular probes on nano-carriers. Based on the above background, we have designed and prepared a highly sensitive PARACEST MR-Eu-Rhod-rHDL, which can improve the sensitivity of PARACEST method. The advantage of developing bimodular contrast media is that it can complement the two imaging methods of PARACEST and fluorescence. In order to make rHDL contrast agent have CEST effect, we first synthesized a kind of phospholipid containing EU (鈪，

本文編號：2086638