Optoacoustic imaging enhanced by gold nanorods

金纳米棒增强光声成像

• 批准号: 7940027
• 负责人: ALEXANDER A ORAEVSKY
• 金额: $ 8.12万
• 依托单位: FAIRWAY MEDICAL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940027
• 关键词: Acoustics; Advanced Malignant Neoplasm; Animal Model; Animals; Antibodies; Area; Biological; Blood; Blood Vessels; Breast; Breast Cancer Cell; Breast Cancer Detection; Cancer Patient; Cancer cell line; Cancerous; Carcinoma in Situ; Cell Volumes; Cells; Clinic; Clinical Research; Collection; Computer Simulation; Contrast Media; Dependence; Detection; Development; Diagnostic; Diagnostic Imaging; Diagnostic Neoplasm Staging; Diffusion; Dimensions; Dyes; ERBB2 gene; Early Diagnosis; Electron Microscopy; Filtration; Fractionation; Frequencies; Gel; Gelatin; Generations; Genes; Goals; Gold; Hand; Heating; Histology; Hour; Human; Image; Imaging Techniques; Imaging technology; Implant; In Situ; In Vitro; Injection of therapeutic agent; Lasers; Life; Light; Lighting; Low-Level Laser Therapy; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Measures; Mechanics; Membrane Proteins; Metals; Methods; Microscopy; Modeling; Molecular; Molecular Biology; Molecular Sieve Chromatography; Monitor; Mus; Nanotechnology; Normal tissue morphology; Optics; Patients; Phase; Physiologic pulse; Poloxamer; Poloxamers; Polyethylene Glycols; Polymers; Procedures; Property; Relative (related person); Research Personnel; Resolution; SKBR3; Shapes; Signal Transduction; Silicon Dioxide; Simulate; Small Business Innovation Research Grant; Solutions; Source; Specificity; Staging; Suspension substance; Suspensions; System; Technology; Testing; Theoretical model; Thick; Time; Tissues; Toxic effect; Trypan Blue; Tumor Angiogenesis; Tumor stage; Ultrasonic wave; Ultrasonics; Ultrasonography; Variant; Vascular Endothelial Growth Factors; Water; Xenograft procedure; absorption; analytical method; angiogenesis; antiangiogenesis therapy; aqueous; base; bioimaging; cell injury; chemotherapy; imaging modality; in vivo; intravenous injection; irradiation; malignant breast neoplasm; mathematical model; mouse model; nanoparticle; nanoparticulate; nanorod; novel; overexpression; particle; physical model; programs; receptor; research study; response; retinal rods; surfactant; tomography; tumor; tumor growth; two-dimensional; vapor; vaporization; Acoustics; Advanced Malignant Neoplasm; Animal Model; Animals; Antibodies; Area; Biological; Blood; Blood Vessels; Breast; Breast Cancer Cell; Breast Cancer Detection; Cancer Patient; Cancer cell line; Cancerous; Carcinoma in Situ; Cell Volumes; Cells; Clinic; Clinical Research; Collection; Computer Simulation; Contrast Media; Dependence; Detection; Development; Diagnostic; Diagnostic Imaging; Diagnostic Neoplasm Staging; Diffusion; Dimensions; Dyes; ERBB2 gene; Early Diagnosis; Electron Microscopy; Filtration; Fractionation; Frequencies; Gel; Gelatin; Generations; Genes; Goals; Gold; Hand; Heating; Histology; Hour; Human; Image; Imaging Techniques; Imaging technology; Implant; In Situ; In Vitro; Injection of therapeutic agent; Lasers; Life; Light; Lighting; Low-Level Laser Therapy; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Measures; Mechanics; Membrane Proteins; Metals; Methods; Microscopy; Modeling; Molecular; Molecular Biology; Molecular Sieve Chromatography; Monitor; Mus; Nanotechnology; Normal tissue morphology; Optics; Patients; Phase; Physiologic pulse; Poloxamer; Poloxamers; Polyethylene Glycols; Polymers; Procedures; Property; Relative (related person); Research Personnel; Resolution; SKBR3; Shapes; Signal Transduction; Silicon Dioxide; Simulate; Small Business Innovation Research Grant; Solutions; Source; Specificity; Staging; Suspension substance; Suspensions; System; Technology; Testing; Theoretical model; Thick; Time; Tissues; Toxic effect; Trypan Blue; Tumor Angiogenesis; Tumor stage; Ultrasonic wave; Ultrasonics; Ultrasonography; Variant; Vascular Endothelial Growth Factors; Water; Xenograft procedure; absorption; analytical method; angiogenesis; antiangiogenesis therapy; aqueous; base; bioimaging; cell injury; chemotherapy; imaging modality; in vivo; intravenous injection; irradiation; malignant breast neoplasm; mathematical model; mouse model; nanoparticle; nanoparticulate; nanorod; novel; overexpression; particle; physical model; programs; receptor; research study; response; retinal rods; surfactant; tomography; tumor; tumor growth; two-dimensional; vapor; vaporization

DESCRIPTION (provided by applicant): The main objective of this project is to develop a contrast agent to allow noninvasive imaging and monitoring of breast cancer with molecular specificity. The basis of the proposed method is a combination of optoacoustic imaging, nanotechnology and molecular biology of cancer. Laser Optoacoustic Imaging System (LOIS) uses near-infrared laser pulses to generate acoustic sources in tumors and the time-resolved detection of resulting transient ultrasonic waves. Clinical studies on breast cancer patients demonstrated that the combination of pulsed laser excitation (which provides high optical contrast between normal and malignant tissue) with the time-resolved detection of ultrasonic waves (which provides undistorted tomographic information from significant depths of tissue), yields a breast imaging system with capability to detect small tumors in situ. On the other hand, one can predict that some breast tumors may possess materially reduced optoacoustic contrast relative to that currently observed in patients with advanced cancer. These cases include: (1) early cancer stages (tumors with dimensions of 1-3 mm) that do not possess dense microvascular network, and (2) tumors treated with anti-angiogenesis chemotherapy. Therefore, we propose to develop and test a Nanoparticulate Optoacoustic Contrast Agent (NOCA) based on gold nanorods (NR) conjugated to antibodies against breast cancer receptors. Recently we demonstrated that gold nanorods represent a unique optoacoustic contrast agent. The optical absorption in gold nanorods is over 10(8)1/cm, i.e. >1000 times stronger than that of any organic molecules. Average near-IR absorption of cancerous tissue loaded with nanorods in concentration of only 10 nanorods per cell will provide additional noticeable contrast of delta-mu about 0.5 cm(-1) relative to normal tissue. Furthermore, the laser-induced acoustic signal from gold nanorods was found an order of magnitude stronger than an optoacoustic signal from dye-solution with equal absorbance. We propose to develop NOCA to utilize the full diagnostic power of LOIS, expanding its imaging capabilities to early carcinoma in situ and other breast tumors with underdeveloped microvasculature. The Phase-I project should result in the proof of feasibility in animals with simultaneous demonstration of our capability to control bioeffects of laser - nanorod interactions.

描述（由申请人提供）： 该项目的主要目的是开发一种对比剂，以允许以分子特异性对乳腺癌进行非侵入性成像。所提出的方法的基础是癌症的光声成像，纳米技术和分子生物学的组合。激光光声成像系统（LOIS）使用近红外激光脉冲在肿瘤中产生声源，并对产生的瞬时超声波的时间分辨检测。对乳腺癌患者的临床研究表明，脉冲激光激发（在正常组织和恶性组织之间提供了高光学对比度）与超声波（超声波的时间分解检测）（从大量组织的显着深度提供了未呈现的层析图）的结合，可产生乳房成像系统，能够检测小肿瘤的乳房成像。另一方面，可以预测，相对于当前在晚期癌症患者中观察到的乳腺肿瘤可能具有重大减少的光声对比。这些病例包括：（1）早期癌症阶段（尺寸为1-3 mm），不具有密度密集的微血管网络，以及（2）接受抗血管生成化疗治疗的肿瘤。因此，我们建议基于与针对乳腺癌受体的抗体结合的金纳米棒（NR）开发和测试纳米构造的光声对比剂（NOCA）。最近，我们证明金纳米棒代表了独特的光声对比剂。金纳米棒中的光吸收超过10（8）1/cm，即比任何有机分子的光吸收> 1000倍。与正常组织相对于正常组织，每个细胞仅浓度只有10纳米棒的癌组织的平均近红外吸收将提供大约0.5 cm（-1）的其他明显对比度。此外，发现激光诱导的来自金纳米棒的声信号比来自具有相等吸光度的染料溶解的光声信号强的数量级。我们建议开发NOCA，以利用路易斯的完整诊断能力，将其成像能力扩展到早期癌和其他乳腺肿瘤，并具有欠发达的微脉管系统。 I期项目应导致动物可行性的证明，同时证明了我们控制激光 - 纳米棒相互作用的生物效应的能力。