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

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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.