分子イメージングを利用した冠動脈硬化性病変の非侵襲的診断法の開発

气泡免疫脂质体分子显像及超声心动图检测犬左心耳血栓。背景：虽然人们普遍认为左心耳血栓会增加房颤患者发生脑梗死的风险，但其形态无定形，在临床常规超声心动图中难以发现和组织学评价。脂质体是一种纳米粒子，它可以将各种药物输送到靶组织，如气泡，并可以包被与靶分子结合的抗体或肽。研究免疫泡脂质体对犬左心耳血栓的检测作用。方法与结果：采用反相蒸发囊泡法（REV）和超声法制备RGD肽包被泡脂质体（Arg-Gly-Asp）。RGD肽与血栓中大量存在的整合素（αvβ3）具有亲和力。我们结扎麻醉犬左心耳120分钟（n=4）。在超声心动图评估血栓后，首先在超声心动图观察下静脉给予生理盐水作为对照研究（图A）。生理盐水输注10分钟后，我们静脉给狗注射免疫泡脂质体。超声心动图清晰发现左耳附件血栓（图b）。在实验方案结束时获得左心耳样本（图c），其组织学分析显示为血栓。结论：通过添加免疫泡脂质体，可以清晰地识别左心耳血栓。免疫泡脂质体超声心动图为犬左心耳血栓的诊断提供了依据。气泡脂质体靶向分子可能是一种新的超声心动图模式。

Molecular imaging using bubble immune-liposomes and echocardiography to detect thrombus in left atrial appendage in canine hearts.Background : Although the presence of thrombus in left atrial appendage was widely known to increase the risk of cerebral infarction in patients with atrial fibrillation, but its morphology was amorphous and has been difficult for the detection and histological evaluation using the conventional echocardiography in the clinical settings. Liposomes are nanoparticles that can deliver various agents to target tissues such as bubble and could be coated with antibody or peptide binding to the target molecule. We investigated whether immune-bubble liposomes could detect the thrombus in left atrial appendage in dogs.Methods and Results : Bubble liposomes coated with RGD peptide(Arg-Gly-Asp) were prepared by reversephase evaporation vesicle(REV) and sonication methods. RGD peptide has an affinity to integrin(αvβ3) which was abundant in the thrombus. We ligated the left atrial appendage of anesthetic dogs for 120 minutes(n=4). After the identification of thrombus evaluated by echocardiography, firstly we intravenously administed saline under the observation of echocardiography as control study(Figure A). After 10 minutes of the infusion of saline, we intravenously administed immune-bubble lipomes into the dogs. Thrombus in left auricular appendage was clearly identified using echocardiography(Figure B.) Left atrial appendage samples were obtained at the end of the experimental protocol(Figure C.) and its histological analysis revealed to be a thrombus.Conclusion : By adding immune-bubble liposomes, thrombus in left atrial appendage can be clearly recognized. Echocardiography using immune-bubble liposomes provide the diagnostic information of the thrombus in left atrial appendage in dogs. Bubble liposomes targeting to the molecule could be a novel echocardiographic modality.