Optoacoustic system for monitoring biodistribution of nanoparticles in vivo.

描述（由申请人提供）：我们提出光声断层扫描在临床前研究中用于纳米颗粒生物分布的无创和定量分析的新应用。目前正在积极开发新的基于纳米技术的癌症和其他疾病的治疗方法，这些方法具有更高的特异性和更高的治疗潜力。目前迫切需要一种低成本和高灵敏度的仪器，能够监测体内纳米颗粒的增殖和清除，以进行健康安全评估和确定疾病治疗的疗效。目前的非侵入性纳米颗粒检测方法，如磁共振成像和放射成像（即计算机断层扫描及其变体）仍然昂贵，并且许多涉及在临床实践中推进基于纳米技术的药物和治疗策略的企业无法获得。相反，对大量样本进行繁琐的死后分析仍然是进行纳米颗粒生物分布研究的常用方法。光声层析成像技术是一种基于组织的光吸收性和高分辨率超声成像的小动物血管和内脏三维成像技术。由于各种各样的金基和碳基纳米颗粒，以及精选的可生物降解纳米复合物已经或可以被设计成在近红外光谱区域显示出强的光学共振，即所谓的生物透明窗口，它们的少量可以用光声学在体内检测到。在这项工作中，我们提出了利用光声技术进行金纳米棒和碳纳米管在小鼠体内定量生物分布分析的可行性。我们的光声断层扫描系统将检测到在特定波长下，小于器官吸光度1%的吸光度的小体积变化。我们建议在特定器官中建立吸收增加与纳米颗粒浓度之间的相关性，以便对体内纳米颗粒进行定量测量。这将使我们能够定义我们方法的灵敏度限制，并在成本，通用性，灵敏度和分辨率方面展示其优势，并评估其未来商业化的潜力。PI是国际公认的光声成像技术及其商业化的领导者，并将指导纳米技术和光声断层成像方面的高素质专家团队成功完成项目。该技术将引领商用仪器的发展，为目前的非侵入性成像模式（如CT和MRI）提供更便宜、更安全、更通用的替代方案。我们的成像系统将在纳米技术导向的生物工程企业和学术界有很高的需求，应用于新型纳米药物和纳米设备的药代动力学分析、生物分布研究和健康风险评估。

DESCRIPTION (provided by applicant): 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.