Abstract
Targeted, liquid perfluorocarbon nanoparticles are effective agents for acoustic contrast
enhancement of abundant cellular epitopes (e.g., fibrin in thrombi) and for lower prevalence binding sites, such as integrins associated
with tumor neovasculature. In this study, we sought to delineate the quantitative
relationship between the extent of contrast enhancement of targeted surfaces and the
density (and concentration) of bound perfluorocarbon (PFC) nanoparticles. Two dramatically
different substrates were utilized for targeting. In one set of experiments, the surfaces
of smooth, flat, avidin-coated agar disks were exposed to biotinylated nanoparticles
to yield a thin layer of targeted contrast. For the second set of measurements, we
targeted PFC nanoparticles applied in thicker layers to cultured smooth muscle cells
expressing the transmembrane glycoprotein “tissue factor” at the cell surface. An
acoustic microscope was used to characterize reflectivity for all samples as a function
of bound PFC (determined via gas chromatography). We utilized a formulation of low-scattering
nanoparticles having oil-based cores to compete against high-scattering PFC nanoparticles
for binding, to elucidate the dependence of contrast enhancement on PFC concentration.
The relationship between reflectivity enhancement and bound PFC content varied in
a curvilinear fashion and exhibited an apparent asymptote (approximately 16 dB and
9 dB enhancement for agar and cell samples, respectively) at the maximum concentrations
(∼150 μg and ∼ 1000 μg PFOB for agar and cell samples, respectively). Samples targeted
with only oil-based nanoparticles exhibited mean backscatter values that were nearly
identical to untreated samples (<1 dB difference), confirming the oil particles’ low-scattering
behavior. The results of this study indicate that substantial contrast enhancement
with liquid perfluorocarbon nanoparticles can be realized even in cases of partial
surface coverage (as might be encountered when targeting sparsely populated epitopes)
or when targeting surfaces with locally irregular topography. Furthermore, it may
be possible to assess the quantity of bound cellular epitopes through acoustic means.
(E-mail: [email protected])
Key Words
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Article info
Publication history
Published online: April 19, 2007
Accepted:
December 23,
2006
Received in revised form:
December 6,
2006
Received:
August 23,
2006
Identification
Copyright
© 2007 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.
