Pro-Bubbles for Ultrasound Imaging and Treatment of Prostate Cancer

描述（由申请人提供）：微泡造影剂用于增强血管空间的超声图像，因为非造影超声对小血管中的血流仅具有非常弱的敏感性。目前，微泡在临床上被批准用于次优超声心动图中的左心室边界增强，并且在临床前用于病变组织的灌注成像和分子成像。然而，由于其尺寸，微泡不能外渗到组织中，因此不能用作血管外造影剂。最近，我们已经开发出可以从脉管系统外渗的纳米滴全氟己烷乳剂。令人惊讶的是，尽管这些液滴的沸点（沸点= 610摄氏度），但人们发现它们会蒸发并在组织中形成气体沉积物。基于这些知识，我们已经初步形成了液体全氟化碳纳米液滴，其可以用声能转变为微泡（称为“前泡”）。对于这个提议，我们假设，如果我们将已知量的全氟己烷添加到前气泡中，我们可以创建可以外渗的颗粒，然后可以通过超声能量激活以形成微米大小的气泡。可以外渗到血管外空间/组织中的靶向前气泡将能够在微气泡通常无法接近的患病组织（例如微转移）处积聚。在外渗和定位在目标部位后，我们可以使用超声将“前泡”激活成限定尺寸的微泡，用于高灵敏度超声成像。 公共卫生相关性：微泡造影剂与超声一起用于血管内疾病和异常的成像。然而，由于它们的尺寸，微泡不能扩散到血管外以使组织成像。我们建议开发一种靶向液滴或“前气泡”，其足够小以扩散到脉管系统外并靶向患病组织。一旦瞄准患病组织，预气泡就可以通过超声转化为气泡，现在可以对其进行成像。这种前气泡可以使临床医生对迄今为止可能无法识别的非常小的转移性肿瘤进行成像，并最终可以用于使用非侵入性超声技术破坏小肿瘤。这种新的创新方法可能会促进癌症的早期检测和治疗。

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.