Pro-Bubbles for Ultrasound Imaging and Treatment of Prostate Cancer

用于前列腺癌超声成像和治疗的 Pro-Bubbles

基本信息

批准号：
8054784
负责人：
Terry Onichi Matsunaga
金额：
$ 17.71万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8054784
关键词：
Acoustics Acute Albumins Antigen Targeting Binding Biodistribution Blood Vessels Blood flow Cell membrane Cells Clinical Clinical Trials Coagulation Process Contrast Media Deposition Development Dialysis procedure Diffuse Disease Drops Early Diagnosis Early treatment Echocardiography Emulsions Exhibits Extravasation Fluorocarbons Frequencies Furuncles Future Gases Glutamate Carboxypeptidase II Image In Vitro Individual Inflammation Ischemic Stroke Knowledge Label Left Ligands Lipids Liposomes Liquid substance Malignant Neoplasms Malignant neoplasm of prostate Methodology Microbubbles Microcirculation Micrometastasis Neoplasm Metastasis Oils Perfusion Pharmaceutical Preparations Polymers Prostatic Neoplasms Rupture Shock Site Speed System Techniques Technology Testing Therapeutic Therapeutic Agents Thrombus Time Tissues Ultrasonic Therapy Ultrasonics Ultrasonography Ventricular Violence Work angiogenesis base design electric impedance in vivo innovation interest molecular imaging nanoDroplet nanometer nanoscale neoplastic cell optical imaging particle perfluorohexane pressure public health relevance receptor sound submicron theranostics tool tumor uptake

项目摘要

DESCRIPTION (provided by applicant): Microbubble contrast agents are used to enhance ultrasound images of the vascular space, as non-contrast ultrasound is only very weakly sensitive to blood flow in small vessels. Currently, microbubbles are approved clinically for left ventricular border enhancement in sub-optimal echocardiography, and are used pre-clinically for perfusion imaging and molecular imaging of diseased tissue. However, due to their size, microbubbles cannot extravasate into the tissue and therefore cannot be used as extravascular contrast agents. Recently, we have developed nanodroplet perfluorohexane emulsions that can extravasate out of the vasculature. Surprisingly, despite their boiling point (bp = 610 C) these droplets were found to vaporize and form gas deposits in tissue. Based upon this knowledge, we have preliminarily formed liquid perfluorocarbon nanodroplets which can be turned into microbubbles with acoustic energy (referred to as "pro-bubbles"). For this proposal, we hypothesize that if we add a known amount of perfluorohexane to a pro-bubble, we can create a particle which can extravasate, and then can be activated by ultrasound energy to form a micron-sized gas bubble. A targeted pro-bubble which can extravasate into the extravascular space/tissue will be able to accumulate at diseased tissue such as micrometastases, which would not normally be accessible by microbubbles. After extravasation and localization at a target site, we can use ultrasound to activate the "pro- bubble" into a microbubble of defined size for high-sensitivity ultrasound imaging. PUBLIC HEALTH RELEVANCE: Microbubble contrast agents are used with ultrasound to image for disease and abnormalities inside the vasculature. However, because of their size, microbubbles cannot diffuse outside the vessels to image tissue. We propose the development of a targeted liquid drop or "pro-bubble" which is small enough to diffuse outside the vasculature and target diseased tissue. Once targeted to diseased tissue, the pro-bubble can be converted to a bubble by ultrasound where it can now be imaged. This pro-bubble could allow clinicians to image very small metastatic tumors that heretofore may not be identified and could eventually be used to destroy the small tumors using non-invasive ultrasound techniques. This new and innovative methodology could potentially advance early detection and treatment of cancer.

描述（由申请人提供）：微气泡对比剂用于增强血管空间的超声图像，因为非对比度超声仅对小血管中的血液流动非常弱。当前，微泡是在临床上批准的，用于超超声心动图的左心室边界增强，并在临时临时用于灌注成像和疾病组织的分子成像。但是，由于它们的大小，微泡不能渗入组织中，因此不能用作血管外造影剂。最近，我们开发了纳米圆形的全氟己烷乳液，可以从脉管系统中渗出。令人惊讶的是，尽管它们的沸点（BP = 610 C）发现这些液滴在组织中蒸发并形成气体沉积物。基于这些知识，我们已经初步形成的液体全氟碳纳米光子可以将其变成具有声能的微泡（称为“ Pro-Bubbles”）。对于此提案，我们假设，如果我们向贝尔布尔添加已知数量的全氟己烷，我们可以创建一个可以外出的粒子，然后可以通过超声能量激活以形成微米大小的气泡。一个可以渗入血管外空间/组织的靶向前泡，将能够在患病组织（例如微型转移）上积累，而微泡通常无法通过微生物来访问。在目标部位进行渗出和定位之后，我们可以使用超声将“泡泡”激活到定义大小的微泡中，以实现高敏感性超声成像。公共卫生相关性：超声造影剂与超声使用脉管系统内部的疾病和异常形象。但是，由于它们的大小，微泡无法在容器外部扩散到图像组织。我们提出了有针对性的液滴或“泡泡”的发展，该液滴或“泡泡”足够小，可以在脉管系统外扩散并靶向患病组织。一旦靶向患病的组织，就可以通过超声将其转换为气泡，现在可以对其进行成像。这种泡沫可以使临床医生能够成像迄今无法鉴定出来的非常小的转移性肿瘤，并最终可以使用非侵入性超声技术来破坏小肿瘤。这种新的创新方法可以潜在地提高对癌症的早期检测和治疗。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（3）

Formulation and acoustic studies of a new phase-shift agent for diagnostic and therapeutic ultrasound.

DOI：
10.1021/la2013705
发表时间：
2011-09-06
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
0
作者：
Sheeran PS;Luois S;Dayton PA;Matsunaga TO
通讯作者：
Matsunaga TO

Decafluorobutane as a phase-change contrast agent for low-energy extravascular ultrasonic imaging.

DOI：
10.1016/j.ultrasmedbio.2011.05.021
发表时间：
2011-09
期刊：
ULTRASOUND IN MEDICINE AND BIOLOGY
影响因子：
2.9
作者：
Sheeran, Paul S.;Wong, Vincent P.;Luois, Samantha;McFarland, Ryan J.;Ross, William D.;Feingold, Steven;Matsunaga, Terry O.;Dayton, Paul A.
通讯作者：
Dayton, Paul A.

Design of ultrasonically-activatable nanoparticles using low boiling point perfluorocarbons.

DOI：
10.1016/j.biomaterials.2012.01.021
发表时间：
2012-04
期刊：
BIOMATERIALS
影响因子：
14
作者：
Sheeran, Paul S.;Luois, Samantha H.;Mullin, Lee B.;Matsunaga, Terry O.;Dayton, Paul A.
通讯作者：
Dayton, Paul A.