Optoacoustic imaging enhanced by gold nanorods

金纳米棒增强光声成像

• 批准号: 7289022
• 负责人: ALEXANDER A ORAEVSKY
• 金额: $ 67.16万
• 依托单位: FAIRWAY MEDICAL TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7289022
• 关键词: athymic mouse; bioimaging /biomedical imaging; biomaterial compatibility; breast neoplasm /cancer diagnosis; cell line; contrast media; disease /disorder model; drug screening /evaluation; early diagnosis; gold; growth factor receptors; immunoconjugates; lasers; mathematical model; molecular pathology; nanotechnology; optics; phantom model; technology /technique development; temperature; tomography; vascular endothelial growth factors

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）： 该项目的主要目标是开发一种造影剂，以实现分子特异性乳腺癌的无创成像和监测。该方法的基础是光声成像、纳米技术和癌症分子生物学的结合。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，并对由此产生的瞬态超声波进行时间分辨检测。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高光学对比度）与超声波的时间分辨检测（从组织的重要深度提供不失真的断层扫描信息）相结合，产生了能够原位检测小肿瘤的乳腺成像系统。另一方面，我们可以预测，与目前在晚期癌症患者中观察到的情况相比，某些乳腺肿瘤的光声对比度可能会大大降低。这些病例包括：（1）早期癌症阶段（尺寸为1-3毫米的肿瘤），不具有致密的微血管网络，以及（2）接受抗血管生成化疗治疗的肿瘤。因此，我们建议开发和测试一种基于金纳米棒（NR）与乳腺癌受体抗体结合的纳米颗粒光声造影剂（NOCA）。最近我们证明金纳米棒代表了一种独特的光声造影剂。金纳米棒的光学吸收超过 10(8)1/cm，即比任何有机分子强 1000 倍以上。每个细胞仅装载 10 个纳米棒的癌组织的平均近红外吸收将提供相对于正常组织约 0.5 cm(-1) 的额外显着对比度 delta-mu。此外，发现来自金纳米棒的激光诱导声信号比来自具有相同吸光度的染料溶液的光声信号强一个数量级。我们建议开发 NOCA 以利用 LOIS 的全部诊断能力，将其成像能力扩展到早期原位癌和其他微血管发育不良的乳腺肿瘤。第一阶段项目应该证明在动物身上的可行性，同时证明我们控制激光-纳米棒相互作用的生物效应的能力。