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Proceedings Paper

Photoacoustic molecular imaging using single walled carbon nanotubes in living mice
Author(s): Adam de la Zerda; Cristina Zavaleta; Shay Keren; Srikant Vaithilingam; Sunil Bodapati; Robert Teed; Zhuang Liu; Jelena Levi; Bryan R. Smith; Te-Jen Ma; Omer Oralkan; Zhen Cheng; Xiaoyuan Chen; Hongjie Dai; Butrus T. Khuri-Yakub; Sanjiv S. Gambhir
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Paper Abstract

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.

Paper Details

Date Published: 12 February 2009
PDF: 12 pages
Proc. SPIE 7177, Photons Plus Ultrasound: Imaging and Sensing 2009, 717725 (12 February 2009); doi: 10.1117/12.806497
Show Author Affiliations
Adam de la Zerda, Stanford Univ. (United States)
Cristina Zavaleta, Stanford Univ. (United States)
Shay Keren, Stanford Univ. (United States)
Srikant Vaithilingam, Stanford Univ. (United States)
Sunil Bodapati, Stanford Univ. (United States)
Robert Teed, Stanford Univ. (United States)
Zhuang Liu, Stanford Univ. (United States)
Jelena Levi, Stanford Univ. (United States)
Bryan R. Smith, Stanford Univ. (United States)
Te-Jen Ma, Stanford Univ. (United States)
Omer Oralkan, Stanford Univ. (United States)
Zhen Cheng, Stanford Univ. (United States)
Xiaoyuan Chen, Stanford Univ. (United States)
Hongjie Dai, Stanford Univ. (United States)
Butrus T. Khuri-Yakub, Stanford Univ. (United States)
Sanjiv S. Gambhir, Stanford Univ. (United States)

Published in SPIE Proceedings Vol. 7177:
Photons Plus Ultrasound: Imaging and Sensing 2009
Alexander A. Oraevsky; Lihong V. Wang, Editor(s)

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