Entwicklung und Evaluierung neuer niedrig-molekularer Sonden für die Charakterisierung von Gefäßerkrankungen mittels der Magnetresonanztomographie

尽管在诊断和治疗方面取得了进步，但心血管疾病仍然是西方世界的主要死亡原因。动脉粥样硬化和主动脉瘤是工业化国家和发展中国家导致死亡的主要原因之一。动脉管壁在这些病变的发生和发展中起着至关重要的作用。亚临床和无症状疾病的长期病程在出现症状或危及生命的并发症之前打开了一个诊断窗口。这个项目研究的假设是，在分子水平上对动脉血管壁的活体评估将允许对早期病理性血管壁变化的生物学特征进行描述，从而改善血管疾病的分期，并能够更准确地监测治疗反应。为了实现这一目标，将开发用于磁共振成像(MRI)检测的新型小分子探针，并在不同的疾病模型中进行研究。探针将首先在体外和体内表征它们的结合和药代动力学特性。随后，将利用这些探针在体内研究靶蛋白在动脉粥样硬化和主动脉瘤发生发展中的作用。该项目的重点将是评估这些探头在疾病早期发现、疾病发展阶段和监测治疗反应方面的有用性。

Despite advances in diagnosis and treatment, cardiovascular diseases remain the leading cause of death in the western world. Atherosclerosis and aortic aneurysms are among the leading causes of mortality in industrialised and developing nations. The arterial vessel wall plays a crucial role in the onset and development of these pathologies. The prolonged course of subclinical and asymptomatic disease opens a diagnostic window before symptoms or life threatening complications can occur. This project investigates the hypothesis that the in vivo assessment of the arterial vessel wall on a molecular level will allow a biological characterisation of early pathological vessel wall changes and thereby improve the staging of vascular diseases and enable more accurate monitoring of therapy response. To achieve this aim, novel small molecular probes for detection with magnetic resonance imaging (MRI) will be developed and investigated in different disease models. Probes will first be characterised in vitro and in vivo concerning their binding and pharmacokinetic properties. Subsequently, the role of the targeted proteins during the development of atherosclerosis and aortic aneurysms will be investigated in vivo with these probes. The focus of this project will be on the evaluation of the usefulness of these probes for early disease detection, staging of disease development and monitoring of response to treatment.