Family of enhanced photoacoustic imaging agents for high-sensitivity and multiplexing studies in living mice.

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.

[1]  Sanjiv S. Gambhir,et al.  AMIDE: A Free Software Tool for Multimodality Medical Image Analysis , 2003 .

[2]  Qizhi Zhang,et al.  Gold nanoparticles as a contrast agent for in vivo tumor imaging with photoacoustic tomography , 2009, Nanotechnology.

[3]  Massoud Motamedi,et al.  High sensitivity of in vivo detection of gold nanorods using a laser optoacoustic imaging system. , 2007, Nano letters.

[4]  Sheng-Wen Huang,et al.  Targeted gold nanorod contrast agent for prostate cancer detection by photoacoustic imaging , 2007 .

[5]  Xinmai Yang,et al.  Photoacoustic tomography of a rat cerebral cortex in vivo with au nanocages as an optical contrast agent. , 2007, Nano letters.

[6]  Te-Jen Ma,et al.  Design, synthesis, and imaging of an activatable photoacoustic probe. , 2010, Journal of the American Chemical Society.

[7]  Stanislav Emelianov,et al.  Multiwavelength photoacoustic imaging and plasmon resonance coupling of gold nanoparticles for selective detection of cancer. , 2009, Nano letters.

[8]  Vasilis Ntziachristos,et al.  Multispectral opto-acoustic tomography of deep-seated fluorescent proteins in vivo , 2009 .

[9]  Sanjiv S Gambhir,et al.  A pilot toxicology study of single-walled carbon nanotubes in a small sample of mice. , 2008, Nature nanotechnology.

[10]  Sheng-Wen Huang,et al.  Indocyanine-green-embedded PEBBLEs as a contrast agent for photoacoustic imaging. , 2007, Journal of biomedical optics.

[11]  H. Dai,et al.  Carbon nanotubes in biology and medicine: In vitro and in vivo detection, imaging and drug delivery , 2009, Nano research.

[12]  Zhuang Liu,et al.  Carbon nanotubes as photoacoustic molecular imaging agents in living mice. , 2008, Nature nanotechnology.

[13]  V. Ntziachristos,et al.  Molecular imaging by means of multispectral optoacoustic tomography (MSOT). , 2010, Chemical reviews.

[14]  Jan Laufer,et al.  Three-dimensional noninvasive imaging of the vasculature in the mouse brain using a high resolution photoacoustic scanner. , 2009, Applied optics.

[15]  O. Oralkan,et al.  P6A-4 A Co-Axial Scanning Acoustic and Photoacoustic Microscope , 2007, 2007 IEEE Ultrasonics Symposium Proceedings.

[16]  H. Dai,et al.  In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. , 2020, Nature nanotechnology.

[17]  Weibo Cai,et al.  Circulation and long-term fate of functionalized, biocompatible single-walled carbon nanotubes in mice probed by Raman spectroscopy , 2008, Proceedings of the National Academy of Sciences.

[18]  A. Bell.  On the production and reproduction of sound by light , 1880, American Journal of Science.

[19]  Sanjiv S Gambhir,et al.  Advanced contrast nanoagents for photoacoustic molecular imaging, cytometry, blood test and photothermal theranostics. , 2011, Contrast media & molecular imaging.

[20]  Xueding Wang,et al.  Picomolar sensitivity MRI and photoacoustic imaging of cobalt nanoparticles , 2009, Proceedings of the National Academy of Sciences.

[21]  Yannis M Paulus,et al.  Photoacoustic ocular imaging. , 2010, Optics letters.

[22]  Jung-Taek Oh,et al.  Three-dimensional imaging of skin melanoma in vivo by dual-wavelength photoacoustic microscopy. , 2006, Journal of biomedical optics.

[23]  V. Zharov,et al.  Golden carbon nanotubes as multimodal photoacoustic and photothermal high-contrast molecular agents. , 2009, Nature nanotechnology.

[24]  Adam de la Zerda,et al.  Ultrahigh sensitivity carbon nanotube agents for photoacoustic molecular imaging in living mice. , 2010, Nano letters.

[25]  Lihong V. Wang,et al.  Functional photoacoustic microscopy for high-resolution and noninvasive in vivo imaging , 2006, Nature Biotechnology.

[26]  Lihong V. Wang.  Multiscale photoacoustic microscopy and computed tomography. , 2009, Nature photonics.

[27]  Geng Ku,et al.  Noninvasive imaging of hemoglobin concentration and oxygenation in the rat brain using high-resolution photoacoustic tomography. , 2006, Journal of biomedical optics.

[28]  Jesse V. Jokerst,et al.  A Brain Tumor Molecular Imaging Strategy Using A New Triple-Modality MRI-Photoacoustic-Raman Nanoparticle , 2011, Nature Medicine.