We propose novel application of optoacoustic tomography for non-invasive and quantitative analysis of nanoparticle biodistribution in preclinical research. Novel nanotechnology-based treatments of cancer and other diseases with increased specificity and enhanced therapeutic potential are being actively developed at present. There is a pressing need for low-cost and high-sensitivity instrumentation capable of monitoring proliferation and clearance of nanoparticles in vivo to perform health safety assessments and determine efficacy of disease treatments. Current non-invasive methods of nanoparticle detection, such as magnetic resonance imaging and radiological imaging (i.e. computer tomography and its variants) remain expensive and are not accessible to many businesses involved in advancing nanotechnology-based drugs and therapeutic strategies in clinical practice. Instead, tedious post-mortem analysis of numerous samples remains a common method to perform nanoparticle biodistribution studies. Optoacoustic tomography is a novel imaging technology based on optical absorptivity of tissues and high resolution of ultrasound to produce three-dimensional images of vasculature and internal organs in small animals. Since a wide variety of gold and carbon-based nanoparticles, as well as select biodegradable nano- complexes already exhibit or can be engineered to display strong optical resonances in a near-infrared spectral region, a so-called biological transparency window, their small quantities can be detected in vivo with optoacoustics. In this work, we propose to demonstrate feasibility of using optoacoustic technology to perform quantitative biodistribution analysis of gold nanorods and carbon nanotubes in mice. Our optoacoustic tomography system will detect small volumetric changes in absoprtivity corresponding to less than 1 % of an organ absorbance at a specific wavelength. We propose to establish a correlation between absorption increase and a concentration of nanoparticles in a particular organ to allow quantitative measurements of nanoparticles in vivo. This will allow us to define sensitivity limits of our method and demonstrate its benefits in terms of cost, versatility, sensitivity and resolution and assess its potential for a future commercialization. The PI is an internationally recognized leader in optoacoustic imaging technology and its commercialization and will guide the team of highly qualified experts in nanotechnology and optoacoustic tomography towards successful completion of a project. The proposed technology will lead towards commercial instrumentation that will provide a significantly cheaper, safer and more versatile alternative to current non invasive imaging modalities, such as CT and MRI. Our imaging system will have a high demand in a nanotechnology-oriented bioengineering businesses and academic circles with applications in pharmacokinetics analysis, biodistribution studies and health risk assessments of novel nano-drugs and nano-devices.
Public Health Relevance: Efficient and affordable imaging technologies capable of non-invasive and highly sensitive imaging of nanoparticles in vivo are needed to perform health risk assessment and biodistribution analysis of nanoparticles and novel nanotechnology-based drugs. Here we demonstrate that optoacoustic tomography is capable of detecting small quantities of carbon and gold nanoparticles and monitor their proliferation in vivo. We propose to define sensitivity of optoacoustic tomography and calibrate the imaging system to allow quantitave measurements of nanoparticle concentrations directly in small animals. Novel, inexpensive and reliable imaging modality is proposed to empower businesses and non-profit researchers interested in developing nanotechnology-based drugs and disease treatments, analyzing health risks presented by nanoparticles and developing strategies to reduce adverse effects associated with nanoparticle presence.
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