Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Palo Alto, California 94305, USA.
ACS Nano. 2012 Jun 26;6(6):4694-701. doi: 10.1021/nn204352r. Epub 2012 May 31.
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 "flavors" of SWNT-dye nanoparticles. In particular, SWNTs that were coated with either QSY(21) (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 α(v)β(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.
光声成像是一种独特的模式，在很大程度上克服了光学成象的分辨率和深度限制，同时保持相对较高的对比度。然而，由于许多疾病不会表现出内源性光声对比，因此开发能够靶向病变组织的外源性光声对比剂是至关重要的。在这里，我们提出了一类基于小分子光学染料与单壁碳纳米管（SWNT-染料）结合的新型光声对比剂。我们使用不同的光学染料合成了五种不同的 SWNT-染料对比剂，制备了五种“风味”的 SWNT-染料纳米粒子。特别是，用 QSY（21）（SWNT-QSY）或吲哚菁绿（SWNT-ICG）包被的 SWNTs 在活体动物中表现出比普通 SWNTs 高出 100 倍的光声对比，达到亚纳摩尔级的灵敏度。然后，我们将 SWNT-染料缀合物与环状 Arg-Gly-Asp 肽缀合，以分子靶向与肿瘤血管生成相关的α（v）β（3）整合素。将这些肿瘤靶向成像剂静脉注射到荷瘤小鼠中，与注射非靶向对比剂的小鼠相比，肿瘤中的光声信号显著增强。最后，我们能够在同一位置皮下注射两种粒子的活体动物中，对 SWNT-QSY 和 SWNT-ICG 的光声信号进行光谱分离，为体内多通道研究开辟了可能性。
