12 February 2009 Photoacoustic molecular imaging using single walled carbon nanotubes in living mice
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Photoacoustic molecular imaging is an emerging technology offering non-invasive high resolution imaging of the molecular expressions of a disease using a photoacoustic imaging agent. Here we demonstrate for the first time the utility of single walled carbon nanotubes (SWNTs) as targeted imaging agents in living mice bearing tumor xenografts. SWNTs were conjugated with polyethylene-glycol-5000 connected to Arg-Gly-Asp (RGD) peptide to target the αvβ3 integrin that is associated with tumor angiogenesis. In-vitro, we characterized the photoacoustic spectra of the particles, their signal linearity and tested their uptake by αvβ3-expressing cells (U87MG). The photoacoustic signal of SWNTs was found not to be affected by the RGD conjugation to the SWNTs and was also found to be highly linear with concentration (R2 = 0.9997 for 25-400nM). The cell uptake studies showed that RGD-targeted SWNTs gave 75% higher photoacoustic signal than non-targeted SWNTs when incubated with U87MG cells. In-vivo, we measured the minimal detectable concentration of SWNTs in living mice by subcutaneously injecting SWNTs at increasing concentrations. The lowest detectable concentration of SWNTs in living mice was found to be 50nM. Finally, we administered RGDtargeted and non-targeted SWNTs via the tail-vein to U87MG tumor-bearing mice (n=4 for each group) and measured the signal from the tumor before and up to 4 hours post-injection. At 4 hours post-injection, tumors of mice injected with RGD-targeted SWNTs showed 8 times higher photoacoustic signal compared with mice injected with non-targeted SWNTs. These results were verified ex-vivo using a Raman microscope that is sensitive to the SWNTs Raman signal.
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Adam de la Zerda, Adam de la Zerda, Cristina Zavaleta, Cristina Zavaleta, Shay Keren, Shay Keren, Srikant Vaithilingam, Srikant Vaithilingam, Sunil Bodapati, Sunil Bodapati, Robert Teed, Robert Teed, Zhuang Liu, Zhuang Liu, Jelena Levi, Jelena Levi, Bryan R. Smith, Bryan R. Smith, Te-Jen Ma, Te-Jen Ma, Omer Oralkan, Omer Oralkan, Zhen Cheng, Zhen Cheng, Xiaoyuan Chen, Xiaoyuan Chen, Hongjie Dai, Hongjie Dai, Butrus T. Khuri-Yakub, Butrus T. Khuri-Yakub, Sanjiv S. Gambhir, Sanjiv S. Gambhir, "Photoacoustic molecular imaging using single walled carbon nanotubes in living mice", Proc. SPIE 7177, Photons Plus Ultrasound: Imaging and Sensing 2009, 717725 (12 February 2009); doi: 10.1117/12.806497; https://doi.org/10.1117/12.806497

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