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

被引：132

作者：

Lobatto, Mark E. ^{[1
,2
]}

Fayad, Zahi A. ^{[1
,2
]}

Silvera, Stephane ^{[1
,2
]}

Vucic, Esad ^{[1
,2
]}

Calcagno, Claudia ^{[1
,2
]}

Mani, Venkatesh ^{[1
,2
]}

Dickson, Stephen D. ^{[1
,2
]}

Nicolay, Klaas ^{[3
]}

Banciu, Manuela ^{[4
]}

Schiffelers, Raymond M. ^{[4
]}

Metselaar, Josbert M. ^{[4
]}

van Bloois, Louis ^{[4
]}

Wu, Hai-Shan ^{[6
]}

Fallon, John T. ^{[6
]}

Rudd, James H. ^{[1
,2
,5
]}

Fuster, Valentin ^{[7
,8
,9
]}

Fisher, Edward A. ^{[10
,11
]}

Storm, Gert ^{[4
]}

Mulder, Willem J. M. ^{[1
,2
]}

机构：

[1] Mt Sinai Sch Med, Translat & Mol Imaging Inst, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Imaging Sci Labs, New York, NY 10029 USA

[3] Eindhoven Univ Technol, Dept Biomed Engn, Biomed NMR, NL-5600 MB Eindhoven, Netherlands

[4] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Pharmaceut, NL-3584 CA Utrecht, Netherlands

[5] Addenbrookes Hosp, Div Cardiovasc Med, Cambridge CB2 2QQ, England

[6] Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA

[7] Mt Sinai Heart, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, Mt Sinai Med Ctr, New York, NY 10029 USA

[8] Mt Sinai Heart, Zena & Michael Wiener Cardiovasc Inst, New York, NY 10029 USA

[9] Ctr Nacl Invest Cardiovasc Carlos III CNIC, E-28029 Madrid, Spain

[10] NYU, Sch Med, Dept Med Cardiol, New York, NY 10016 USA

[11] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA

来源：

MOLECULAR PHARMACEUTICS | 2010年 / 7卷 / 06期

基金：

美国国家科学基金会;

关键词：

MRI; FDG-PET; multifunctional liposomes; atherosclerosis; rabbits; glucocorticoids; POSITRON-EMISSION-TOMOGRAPHY; CONTRAST-ENHANCED MRI; LIPOSOMAL PREDNISOLONE PHOSPHATE; MELANOMA-BEARING MICE; PLAQUE INFLAMMATION; B16; MELANOMA; IN-VIVO; ONCOLOGICAL APPLICATIONS; ANTITUMOR-ACTIVITY; F-18-FDG PET;

D O I：

10.1021/mp100309y

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

100103 [病原生物学]; 100218 [急诊医学];

摘要：

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. F-18-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.

引用

页码：2020 / 2029

页数：10

共 44 条

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