Optoacoustic imaging enhanced by gold nanorods

描述(由申请人提供)： 该项目的主要目标是开发一种造影剂，以实现具有分子特异性的乳腺癌的非侵入性成像和监测。提出的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，并对产生的瞬时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)与时间分辨超声波检测(从组织的显著深处提供不失真的断层扫描信息)相结合，产生了一种能够原位检测小肿瘤的乳腺成像系统。另一方面，人们可以预测，与目前在晚期癌症患者中观察到的相比，一些乳腺肿瘤的光声对比度可能会大幅降低。这些病例包括：(1)没有致密微血管网的早期癌(肿瘤大小为1-3 mm)和(2)接受抗血管生成化疗的肿瘤。因此，我们建议开发和测试一种基于金纳米棒(NR)的纳米颗粒光声造影剂(NOCA)，该纳米棒与抗乳腺癌受体的抗体相连。最近，我们证明了金纳米棒是一种独特的光声造影剂。金纳米棒的光吸收超过10(8)1/cm，比任何有机分子的光吸收强1000倍。平均近红外吸收的癌组织负载纳米棒的浓度只有10纳米棒每个细胞将提供额外的显著对比度约0.5厘米(-1)与正常组织。此外，金纳米棒的激光诱导声信号比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以充分利用LOIS的诊断能力，将其成像能力扩展到早期原位癌和其他微血管发育不全的乳腺肿瘤。第一阶段项目应该在动物身上证明可行性，同时证明我们有能力控制激光-纳米棒相互作用的生物效应。

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.