In Vivo Detection of Nanoparticles in Mouse Cancer Using an Integrated Photoacoustic Micro-Ultrasound System
1. In vivo detection of nanoparticles in mouse
John Sun, Andrew Heinmiller,
Dave Bates, Andrew Needles,
Catherine Theodoropoulos
cancer using an integrated photoacoustic VisualSonics Inc., Toronto, ON,
Canada
micro-ultrasound system
Introduction: • Concentrations used for gold nanoparticles were
• Photoacoustics is a rapidly-emerging imaging 1.5 mgAu/mL and for fluorescent agents were • Tumor • Mammary fat pad
modality that combines the sensitivity of optical 20 nmol/mL
and resolution of ultrasound imaging • Laser fluence was kept under 4 mJ/cm2 to avoid
• A state-of-the-art photoacoustic system was deformation of the nanoparticles
recently developed that co-registers high-resolution • Each nanoparticle’s respective peak absorption
micro-ultrasound and high sensitivity photoacoustic wavelength was used for photoacoustic imaging
images
Mouse Study: Figure 2. Much higher amount of gold nanorod accumulation in the
• Nano-sized agents present an enormous potential
• Female hairless SCID mice with subcutaneous tumor was observed than compared to the mammary fat pad.
in many research fields and can be imaged with
tumors were imaged
photoacoustics
• 150 µL of 1.5 mgAu/mL of gold nanorods (Ntracker, A)
1mm
B)
1mm
Objectives: Nanopartz) were injected intravenously through the
tail vein
• To assess the utility of various nano-sized agents as
photoacoustic contrast agents • Tumor photoacoustic intensity was measured up to
3 hours post injection 0 min
• To assess gold nanorod imaging in mouse tumor
• 50 µL of ultrasound contrast (Vevo MicroMarker®
• To compare tumor ultrasound contrast flow and PA intensity∆ = 9.8 PA intensity∆ = 1.1
Contrast Agent, VisualSonics) was injected
photoacoustic gold nanorod accumulation
intravenously to assess tumor perfusion 1mm 1mm
• Tumor perfusion was correlated to gold nanorod
accumulation in the tumor
• Gold nanorod accumulations in the tumor and 180 min
mammary fat pad were compared
Results: PE = 19.6 PE = 82.3
• In the vessel phantom study, gold nanorods showed
the greatest photoacoustic intensity (Figure 1a).
Though fluorescent agents yield lower intensities,
however they were significantly greater than that
observed in saline
Figure 3. A) Tumor with high amount gold nanorod accumulation and
• Following intravenous injection of gold nanorods, low ultrasound contrast perfusion B) Tumor with low amount of gold
photoacoustic intensity showed a greater increase nanorod accumulation and high ultrasound contrast perfusion.
Methods: in the tumor relative to the mammary fat pad
(Figure 2)
Photoacoustics (Vevo® LAZR System, VisualSonics, Summary:
Toronto, Canada): • Amount of gold nanorod accumulation in the
• The Vevo LAZR photoacoustic imaging system can
tumor showed an inverse correlation to tumor
• Tuneable laser (680-970 nm) detect and quantify gold nanorod accumulation in
perfusion measured by ultrasound contrast imaging
• Integrated fibre optics linear array (Fc = 21 MHz) mouse tumors.
(Figure 1B)
photoacoustic transducer (LZ250, VisualSonics) • Preferential accumulation of gold nanorods was
observed in the tumor, likely due to its leaky
Vessel Phantom Study vasculature
• Nanoparticle agents filled PE20 tubing and were • Perfusion assessed by ultrasound contrast imaging
imaged in water appeared to be inversely correlated to the amount
• Nanoparticles used were: of gold nanorod accumulation in the tumor
» Gold nanoparticles: Gold nanorod (Nanopartz, • Florescent agents can be detected with
Loveland, California), gold nanoshell photoacoustic imaging, hence they may be viable
(Nanospectra, Houston, Texas) photoacoustic contrast agents
» Fluorescent agents: Angiosense 680 and 750
(PerkinElmer, Waltham, MA), IRDye800 (Li-Cor, Figure 1. A) Photoacoustic intensity of various contrast agents. B)
Correlation between ultrasound contrast perfusion and gold nanorod
Lincoln, Nebraska) accumulation in mouse tumor.
http://www.visualsonics.com/photoacoustic-technology