Development of Molecularly Targeted Ultrasound Contrast Agents for Prostate Cancer Imaging using Bioorthogonal Chemistry

目前用于检测前列腺癌的成像和活检方法具有重大局限性，会影响患者的预后，并可能导致不必要的治疗。这些包括使用无效的治疗方法，或者患者经历的不必要的和改变生活的副作用，导致医疗系统额外和不必要的费用和负担。拟议的研究的目的是通过使用超声成像和新一代靶向造影剂来克服这些限制，这种造影剂与前列腺癌细胞结合，但不与正常组织结合。微泡造影剂利用了一种新的靶向技术，允许他们只收集侵袭性肿瘤，从而产生增强的超声信号。通过这种方法，将有可能正确地识别那些需要立即和更积极的治疗的患者，而不是那些可以选择积极监测的患者。它还将创建一个工具，帮助更好地指导活组织检查，以最大限度地减少抽样错误和重复程序的需要，目前这种情况发生得太频繁了。麦克马斯特大学的一个化学小组和桑尼布鲁克医院的一个超声成像小组合作完成了这个项目，在大多数癌症中心都可以使用超声技术，这使得这种方法在前列腺癌的检测和监测方面是可行的，而且非常有用。来自科学和健康科学领域的学生将以小组形式工作，以实现特定的目标。该提议得到了强有力的初步研究和加拿大一家超声成像公司和一家国家英才中心的积极参与的支持，这些公司的专业知识确保新技术能够迅速从实验室进入临床，并最终进入市场。该项目的结果可能会带来前列腺癌患者诊断方式的转变，同时减少不必要的治疗并改善结果。

Current imaging and biopsy methods for the detection of prostate cancer have major limitations that impact patient outcomesand can lead to unnecessary treatments. These include the use of ineffective therapies, or unnecessary and life-altering sideeffects being experienced by patients, resulting in added and unnecessary expense and burden to the healthcare system.The aim of the proposed study is to overcome these limitations by using ultrasound imaging, together with a new generationof targeted contrast agents that bind to prostate cancer cells, but not to normal tissue. The microbubble contrast agentsutilize a new targeting technology that allows them to collect only in aggressive tumors, resulting in an enhanced ultrasoundsignal. With this approach, it will be possible to properly identify those patients that need immediate and more aggressivetreatment, from those that can opt for active surveillance. It will also create a tool to help better guide biopsies, in order tominimize sampling errors and the need to repeat procedures, which at present happen too frequently. The availability ofultrasound technology in most cancer centers makes this approach both feasible and highly useful for detection andmonitoring of prostate cancer.The project will be accomplished through collaboration between a chemistry group at McMaster University and an ultrasoundimaging group at Sunnybrook Hospital. Students from science and health science fields will work in teams to carry out thespecific aims. The proposal is supported by strong preliminary research and the active participation of a Canadianultrasound imaging company and a national centre of excellence, whose expertise ensure that the new technologies canquickly move from the laboratory to the clinic, and ultimately to the market. The results of this project could bring a paradigmshift in how prostate cancer patients are diagnosed, and at the same time reduce unnecessary treatments and improvingoutcomes.