Topical Application of Activity-based Probes for Visualization of Brain Tumor Tissue

Several investigators have shown the utility of systemically delivered optical imaging probes to image tumors in small animal models of cancer. Here we demonstrate an innovative method for imaging tumors and tumor margins during surgery. Specifically, we show that optical imaging probes topically applied to tumors and surrounding normal tissue rapidly differentiate between tissues. In contrast to systemic delivery of optical imaging probes which label tumors uniformly over time, topical probe application results in rapid and robust probe activation that is detectable as early as 5 minutes following application. Importantly, labeling is primarily associated with peri-tumor spaces. This methodology provides a means for rapid visualization of tumor and potentially infiltrating tumor cells and has potential applications for directed surgical excision of tumor tissues. Furthermore, this technology could find use in surgical resections for any tumors having differential regulation of cysteine cathepsin activity.已有多项研究表明，全身递送的光学成像探针（optical imaging probes）可用于癌症小动物模型的肿瘤成像。本研究展示了一种可用于手术中肿瘤及肿瘤切缘成像的创新方法。具体而言，本研究证实，将光学成像探针局部施用于肿瘤及周围正常组织时，可快速区分不同组织类型。与随时间均匀标记肿瘤的全身递送光学成像探针不同，局部施用探针可实现快速且强效的探针激活，最早可在施用后5分钟内检测到信号。值得注意的是，探针标记主要集中于肿瘤周围间隙。该方法可实现肿瘤及潜在浸润性肿瘤细胞的快速可视化，为肿瘤组织的精准手术切除提供了可行途径。此外，该技术可应用于半胱氨酸组织蛋白酶（cysteine cathepsin）活性存在差异调控的各类肿瘤的手术切除操作。