Pro-Bubbles for Ultrasound Imaging and Treatment of Prostate Cancer

说明(申请人提供)：微泡造影剂用于增强血管空间的超声图像，因为非造影剂对小血管中的血流仅非常微弱的敏感。目前，微泡已被临床批准用于次优超声心动图的左心室边缘增强，并在临床前用于病变组织的灌注成像和分子成像。然而，由于其大小，微泡不能渗入组织，因此不能用作血管外造影剂。最近，我们已经开发出可以从血管系统中渗出的纳米液滴全氟己烷乳剂。令人惊讶的是，尽管它们的沸点(BP=610℃)，这些液滴被发现蒸发并在组织中形成气体沉积。基于这一认识，我们已经初步形成了液体全氟碳纳米液滴，这些液滴可以转变为具有声能的微气泡(称为前气泡)。对于这一提议，我们假设，如果我们将已知数量的全氟己烷添加到前气泡中，我们可以创建一个可以渗出的颗粒，然后可以通过超声波能量激活形成微米大小的气泡。可以外溢到血管外空间/组织的靶向前气泡将能够在病变组织如微转移瘤处积聚，这通常是微泡无法到达的。在目标部位渗出和定位后，我们可以使用超声波将“前气泡”激活成定义大小的微泡，以进行高灵敏度的超声成像。 公共卫生相关性：微泡造影剂与超声一起用于成像血管系统内的疾病和异常。然而，由于其大小，微泡不能扩散到血管外以成像组织。我们建议开发一种靶向液滴或“前气泡”，这种液滴小到足以扩散到血管系统和靶向病变组织之外。一旦定位于病变组织，亲气泡可以通过超声波转化为气泡，现在可以在那里进行成像。这种前气泡可以让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，并最终可以使用非侵入性超声波技术来摧毁这些小肿瘤。这一新的创新方法可能会促进癌症的早期发现和治疗。

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.