478559 Photoacoustic Imaging of cRGD Targeted Nanoparticles in a Lewis Lung Carcinoma Tumor Model

Monday, November 14, 2016
Grand Ballroom B (Hilton San Francisco Union Square)
Tristan L. Lim1, Hoang D. Lu1, Brian K. Wilson1, Shoshana Javitt1, Andrew Heinmiller2 and Robert K. Prud'homme1, (1)Department of Chemical and Biological Engineering, Princeton University, Princeton, NJ, (2)FUJIFILM VisualSonics, Toronto, ON, Canada

Photoacoustic (PA) imaging is a biomedical imaging modality that relies on photon adsorption and processing of resultant pressure waves by conventional ultrasound transducers to construct images in 3D real-time high spatial resolution. Through PA imaging, multiple species can be simultaneously imaged; however, these efforts have been greatly limited by the availability of spectrally separable contrast agents that can be used in vivo. Towards this end, we present here the development of a mixed nanoparticle (NP) system for real-time simultaneous in vivo multiplexed PA imaging. Nineteen water-insoluble organic dyes were screened for poly-ethylene glycol (PEG) coated nanoparticle stability, yielding ten with unique separable absorbance profiles, highly tunable optical properties within the near-infrared window, and in vivo compatibility. This new in vivo compatible mixed-NP system with unique separable absorbance profiles enables advanced PA imaging applications with pharmacokinetic implications. Mixed-sample cRGD peptide surface modified NPs and non-modified NPs were simultaneously tracked in real-time in a murine subcutaneous Lewis lung carcinoma tumor model. Simultaneous imaging of non-modified NPs serves to normalize the effects of active-ligand against passive-NP targeting effects with, for example, 25% surface cRGD modified NPs displaying only 9.8 ± 4 fold higher liver to tumor ratio accumulation levels as opposed to 52 ± 22 fold accumulation levels pre-normalization, questioning the effectiveness of NP targeting. As a result, our new nanoparticle contrast agent tools advance the field of PA imaging with in vivo real-time multiplexed imaging capabilities and pharmacokinetic applications.

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