(541c) Photoacoustic Imaging to Simultaneously Detect the Accumulation of Multiple Contrast Agents within Tumors

Wang, L. Z., Princeton University
Lu, H. D., Princeton University
Lim, T. L., Princeton University
Wilson, B. K., Princeton University
Heinmiller, A., FUJIFILM VisualSonics
Prud'homme, R. K., Princeton University

Modern cancer therapeutics have shifted focus from generic
therapeutics to developing personalized treatment plans for greater safety and
effectiveness.  Since drugs are rapidly
being developed specifically for each cancer phenotype, there is an increased
demand for fast and inexpensive methods to determine cancer phenotypes and
morphologies. Current diagnostic imaging modalities utilizing X-ray CT, MRI,
and PET scans are limited to black-white images that cannot be used to
differentiate multiple disease marker contrast agents at a time. In addition, the
high costs of capital equipment and dangers of excessive imaging associated
with these techniques inhibit their widespread use in diagnostics. Photoacoustic
(PA) imaging, a hybrid light and sounds imaging technique, has shown to be a
safe and inexpensive diagnostic technique with high spatial resolution in 3D. Traditional
PA contrast agents, however, tend to have broad absorption peaks in the NIR
range which renders it difficult to simultaneously image more than one signal
at a time in deep tissue. Here we present the formulation of a series of PA
active NPs with sharp and separable absorbance profiles in the NIR range for
simultaneous multiplexed imaging (Fig.
. PA dyes are encapsulated inside NPs using the controlled self-assembly
mechanism, Flash Nanoprecipitation (FNP). Four new contrast agents, with sharp
absorbance maxima between 600-900 nm, were created by encapsulating a variety
of phthalocyanine derivatives. We were able to concurrently detect the
concentrations of contrast agents mixed together with >95% deconvolution efficacy.
Using these dye particles, we demonstrated that information on tumor morphology
and surrounding blood flow can be acquired simultaneously (Fig. 2). As proof of concept, we co-injected RGD modified NPs and non-modified
NPs with different labeling agents and tracked NP biodistributions for both
particles simultaneously. Using this technology, we accessed the effect of NP
ligand modification on both targeting efficacy onto the tumors and
off-targeting accumulation in the liver using a single animal model. Over
modification of the NPs resulted in rapid liver clearance and poor accumulation
in the tumor; at low modifications, the tumor to liver accumulation ratio is 9.9
± 4.2, while at high RGD modifications the tumor to liver accumulation ratio is
52 ± 22. Our particles enable new quantitative and rapid methods of assessing
nanoparticle biodistributions.