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影响患者结局的主要局限性，并可能导致不必要的治疗。这些包括使用无效的治疗，或不必要的和改变患者生活的副作用，导致医疗保健系统增加和不必要的费用和负担。拟议研究的目的是通过使用超声成像，以及新一代的靶向造影剂，结合前列腺癌细胞，但不结合正常组织来克服这些限制。微泡造影剂利用了一种新的靶向技术，使它们只在侵袭性肿瘤中聚集，从而增强超声信号。有了这种方法，就有可能从那些可以选择积极监测的患者中正确识别出那些需要立即和更积极治疗的患者。它还将创建一个工具来帮助更好地指导活检，以最大限度地减少采样错误和重复程序的需要，目前这种情况太频繁了。超声技术在大多数癌症中心的可用性使得这种方法在检测和监测前列腺癌方面既可行又非常有用。该项目将通过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的合作来完成。来自科学和健康科学领域的学生将在团队中工作，以实现特定的目标。该提案得到了强有力的初步研究的支持，并得到了一家美国超声成像公司和一个国家卓越中心的积极参与，其专业知识确保新技术能够迅速从实验室转移到临床，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范式转变，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.