Multimodal Clinical Imaging To Longitudinally Assess a Nanomedical Anti-Inflammatory Treatment in Experimental Atherosclerosis

作者：Lobatto Mark E; Fayad Zahi A^*; Silvera Stephane; Vucic Esad; Calcagno Claudia; Mani Venkatesh; Dickson Stephen D; Nicolay Klaas; Banciu Manuela; Schiffelers Raymond M; Metselaar Jo**ert M; van Bloois Louis; Wu Hai Shan; Fallon John T; Rudd James H; Fuster Valentin; Fisher Edward A; Storm Gert; Mulder Willem J M

来源：Molecular Pharmaceutics, 2010, 7(6): 2020-2029.

DOI：10.1021/mp100309y

• MRI
• FDG-PET
• multifunctional liposomes
• atherosclerosis
• rabbits
• glucocorticoids

Atherosclerosis is an inflammatory disease causing great morbidity and mortality in the Western world. To increase the anti-inflammatory action and decrease adverse effects of glucocorticoids (PLP), a nanomedicinal liposomal formulation of this drug (L-PLP) was developed and intravenously applied at a dose of 15 mg/kg PLP to a rabbit model of atherosclerosis. Since atherosclerosis is a systemic disease, emerging imaging modalities for assessing atherosclerotic plaque are being developed. (18)F-Fluoro-deoxy-glucose positron emission tomography and dynamic contrast enhanced magnetic resonance imaging, methods commonly used in oncology, were applied to longitudinally assess therapeutic efficacy. Significant anti-inflammatory effects were observed as early as 2 days that lasted up to at least 7 days after administration of a single dose of L-PLP. No significant changes were found for the free PLP treated animals. These findings were corroborated by immunohistochemical analysis of macrophage density in the vessel wall. In conclusion, this study evaluates a powerful two-pronged strategy for efficient treatment of atherosclerosis that includes nanomedical therapy of atherosclerotic plaques and the application of noninvasive and clinically approved imaging techniques to monitor delivery and therapeutic responses. Importantly, we demonstrate unprecedented rapid anti-inflammatory effects in atherosclerotic lesions after the nanomedical therapy.

• 出版日期2010-12