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，因为非造影剂超声对小血管中的血流仅非常弱敏感。目前，微泡已被临床批准用于次优超声心动图左室边界增强，并用于临床前病变组织的灌注成像和分子成像。然而，由于它们的大小，微泡不能外渗到组织中，因此不能用作血管外造影剂。最近，我们已经开发出纳米液滴的全氟己烷乳液，可以渗出血管。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。在此基础上，我们初步形成了液态全氟碳纳米液滴，它可以转化为具有声能的微气泡（称为“亲气泡”）。对于这个提议，我们假设，如果我们在前泡中加入已知数量的全氟己烷，我们可以创造一个可以外溢的粒子，然后可以被超声波能量激活，形成一个微米大小的气泡。靶向前泡可以外渗到血管外空间/组织中，可以在病变组织中积累，如微转移，这通常是微泡无法到达的。外渗并定位于目标部位后，我们可以利用超声将“前泡”激活成确定大小的微泡，进行高灵敏度超声成像。

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.