Family of Enhanced Photoacoustic Imaging Agents for High-Sensitivity and Multiplexing Studies in Living Mice

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• 作者：Adam de la Zerda ; Sunil Bodapati ; Robert Teed ; Salom贸n Y. May ; Scott M. Tabakman ; Zhuang Liu ; Butrus T. Khuri-Yakub ; Xiaoyuan Chen ; Hongjie Dai ; Sanjiv S. Gambhir
• 刊名：ACS Nano
• 出版年：2012
• 出版时间：June 26, 2012
• 年：2012
• 卷：6
• 期：6
• 页码：4694-4701
• 全文大小：508K
• 年卷期：v.6,no.6(June 26, 2012)
• ISSN：1936-086X

文摘

Photoacoustic imaging is a unique modality that overcomes to a great extent the resolution and depth limitations of optical imaging while maintaining relatively high contrast. However, since many diseases will not manifest an endogenous photoacoustic contrast, it is essential to develop exogenous photoacoustic contrast agents that can target diseased tissue(s). Here we present a family of novel photoacoustic contrast agents that are based on the binding of small optical dyes to single-walled carbon nanotubes (SWNT-dye). We synthesized five different SWNT-dye contrast agents using different optical dyes, creating five 鈥渇lavors鈥?of SWNT-dye nanoparticles. In particular, SWNTs that were coated with either QSY₂₁ (SWNT-QSY) or indocyanine green (SWNT-ICG) exhibited over 100-times higher photoacoustic contrast in living animals compared to plain SWNTs, leading to subnanomolar sensitivities. We then conjugated the SWNT-dye conjugates with cyclic Arg-Gly-Asp peptides to molecularly target the 伪_v尾₃ integrin, which is associated with tumor angiogenesis. Intravenous administration of these tumor-targeted imaging agents to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. Finally, we were able to spectrally separate the photoacoustic signals of SWNT-QSY and SWNT-ICG in living animals injected subcutaneously with both particles in the same location, opening the possibility for multiplexing in vivo studies.

Keywords:

carbon nanotubes; SWNT; molecular imaging; photoacoustic imaging; multiplexing