DataSheet_1_Fluorescence Imaging Using Enzyme-Activatable Probes for Real-Time Identification of Pancreatic Cancer.docx

IntroductionRadical resection is the only curative treatment for pancreatic cancer, which is a life-threatening disease. However, it is often not easy to accurately identify the extent of the tumor before and during surgery. Here we describe the development of a novel method to detect pancreatic tumors using a tumor-specific enzyme-activatable fluorescence probe.MethodsTumor and non-tumor lysate or small specimen collected from the resected specimen were selected to serve as the most appropriate fluorescence probe to distinguish cancer tissues from noncancerous tissues. The selected probe was sprayed onto the cut surface of the resected specimen of cancer tissue to acquire a fluorescence image. Next, we evaluated the ability of the probe to detect the tumor and calculated the tumor-to-background ratio (TBR) by comparing the fluorescence image with the pathological extent of the tumor. Finally, we searched for a tumor-specific enzyme that optimally activates the selected probe.ResultsUsing a library comprising 309 unique fluorescence probes, we selected GP-HMRG as the most appropriate activatable fluorescence probe. We obtained eight fluorescence images of resected specimens, among which four approximated the pathological findings of the tumor, which achieved the highest TBR. Finally, dipeptidyl-peptidase IV (DPP-IV) or a DPP-IV-like enzyme was identified as the target enzyme.ConclusionThis novel method may enable rapid and real-time visualization of pancreatic cancer through the enzymatic activities of cancer tissues.

引言：根治性切除是胰腺癌的唯一治愈性治疗方法，而胰腺癌是一种危及生命的疾病。然而，在手术前后准确识别肿瘤的范围往往并非易事。在本研究中，我们描述了一种新型方法，通过使用肿瘤特异性酶激活荧光探针来检测胰腺肿瘤。方法：选取肿瘤和非肿瘤组织裂解物或小块标本，作为最合适的荧光探针，以区分癌组织与非癌组织。所选探针被喷涂在切除标本的切面上，以获取荧光图像。随后，我们评估了探针检测肿瘤的能力，并通过将荧光图像与肿瘤的病理范围进行比较，计算了肿瘤与背景比（TBR）。最后，我们寻找了一种能够最优激活所选探针的肿瘤特异性酶。结果：在包含309种独特荧光探针的文库中，我们选择了GP-HMRG作为最合适的可激活荧光探针。我们获得了8张切除标本的荧光图像，其中4张与肿瘤的病理发现相吻合，并实现了最高的TBR。最终，二肽肽酶IV（DPP-IV）或DPP-IV样酶被确认为目标酶。结论：该新型方法可能通过癌组织的酶活性实现胰腺癌的快速实时可视化。