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

By Adam de la Zerda (1482949), Sunil Bodapati (2070958), Robert Teed (2070961), Salomón Y. May (2070964), Scott M. Tabakman (438868), Zhuang Liu (551357), Butrus T. Khuri-Yakub (475821), Xiaoyuan Chen (322516), Hongjie Dai (357638) and Sanjiv S. Gambhir (1234206)

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<sub>21</sub> (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<sub>v</sub>β<sub>3</sub> 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 <i>in vivo</i> studies

Topics: Biophysics, Medicine, Cell Biology, Neuroscience, Physiology, Pharmacology, Biotechnology, Immunology, Developmental Biology, Cancer, Virology, Chemical Sciences not elsewhere classified, Living MicePhotoacoustic imaging, α v β3 integrin, Enhanced Photoacoustic Imaging Agents, untargeted contrast agent, exogenous photoacoustic contrast agents, photoacoustic contrast, novel photoacoustic contrast agents, SWNT, QSY
Year: 2012
DOI identifier: 10.1021/nn204352r.s001
OAI identifier: oai:figshare.com:article/2510809
Provided by: FigShare
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