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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

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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