Ultrahigh Sensitivity Carbon Nanotube Agents for Photoacoustic Molecular Imaging in Living Mice

• Published in: Nano letters 2010-06, Vol.10 (6), p.2168-2172
• Main Authors: Zerda, Adam de la, Liu, Zhuang, Bodapati, Sunil, Teed, Robert, Vaithilingam, Srikant, Khuri-Yakub, Butrus T, Chen, Xiaoyuan, Dai, Hongjie, Gambhir, Sanjiv Sam
• Format: Article
• Language: English
• Subjects: Acoustics; Animals; Cross-disciplinary physics: materials science; rheology; Exact sciences and technology; Integrins - chemistry; Materials science; Mice; Nanocrystalline materials; Nanoscale materials and structures: fabrication and characterization; Nanotubes; Nanotubes, Carbon; Oligopeptides - chemistry; Photochemistry; Physics
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/nl100890d

Photoacoustic imaging is an emerging 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 novel photoacoustic contrast agent, Indocyanine Green dye-enhanced single walled carbon nanotube (SWNT-ICG). We conjugated this contrast agent with cyclic Arg-Gly-Asp (RGD) peptides to molecularly target the αvβ3 integrins, which are associated with tumor angiogenesis. Intravenous administration of this tumor-targeted contrast agent to tumor-bearing mice showed significantly higher photoacoustic signal in the tumor than in mice injected with the untargeted contrast agent. The new contrast agent gave a markedly 300 times higher photoacoustic contrast in living tissues than previously reported SWNTs, leading to subnanomolar sensitivities. Finally, we show that the new contrast agent can detect ∼20 times fewer cancer cells than previously reported SWNTs.