In Vivo Fluorescence Imaging in the Second Near-Infrared Window with Long Circulating Carbon Nanotubes Capable of Ultrahigh Tumor Uptake

• Published in: Journal of the American Chemical Society Vol. 134; no. 25; pp. 10664 - 10669
• Main Authors: Robinson, Joshua T, Hong, Guosong, Liang, Yongye, Zhang, Bo, Yaghi, Omar K, Dai, Hongjie
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 27-06-2012
• Subjects: Animals; Breast Neoplasms - diagnosis; Contrast Media - pharmacokinetics; Female; Infusion Pumps; Mice; Mice, Inbred BALB C; Nanotubes, Carbon; Polyethylene Glycols - pharmacokinetics; Spectroscopy, Near-Infrared; Time Factors
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja303737a

Cancer imaging requires selective high accumulation of contrast agents in the tumor region and correspondingly low uptake in healthy tissues. Here, by making use of a novel synthetic polymer to solubilize single-walled carbon nanotubes (SWNTs), we prepared a well-functionalized SWNT formulation with long blood circulation (half-life of ∼30 h) in vivo to achieve ultrahigh accumulation of ∼30% injected dose (ID)/g in 4T1 murine breast tumors in Balb/c mice. Functionalization dependent blood circulation and tumor uptake were investigated through comparisons with phospholipid-PEG solubilized SWNTs. For the first time, we performed video-rate imaging of tumors based on the intrinsic fluorescence of SWNTs in the second near-infrared (NIR-II, 1.1–1.4 μm) window. We carried out dynamic contrast imaging through principal component analysis (PCA) to immediately pinpoint the tumor within ∼20 s after injection. Imaging over time revealed increasing tumor contrast up to 72 h after injection, allowing for its unambiguous identification. The 3D reconstruction of the SWNTs distribution based on their stable photoluminescence inside the tumor revealed a high degree of colocalization of SWNTs and blood vessels, suggesting enhanced permeability and retention (EPR) effect as the main cause of high passive tumor uptake of the nanotubes.