title: Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in living mice.
abstract: 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.
authors.affiliation: Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University, Palo Alto, California 94305, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: de la Zerda
authors.forename: Sunil
authors.initials: S
authors.lastname: Bodapati
authors.forename: Robert
authors.initials: R
authors.lastname: Teed
authors.forename: Salomón Y
authors.initials: SY
authors.lastname: May
authors.forename: Scott M
authors.initials: SM
authors.lastname: Tabakman
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Liu
authors.forename: Butrus T
authors.initials: BT
authors.lastname: Khuri-Yakub
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Chen
authors.forename: Hongjie
authors.initials: H
authors.lastname: Dai
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000138:chemical synthesis*; D005456:Fluorescent Dyes; D007089:Image Enhancement / Q000379:methods*; D008422:Materials Testing; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000473:pathology*; D061088:Photoacoustic Techniques / Q000379:methods*; D012680:Sensitivity and Specificity
chemical_list: D003287:Contrast Media; D005456:Fluorescent Dyes; D037742:Nanotubes, Carbon