Takahashi Ryugen, Ishizawa Takeaki, Sato Masumitsu, Inagaki Yoshinori, Takanka Mariko, Kuriki Yugo, Kamiya Mako, Ushiku Tetsuo, Urano Yasuteru, Hasegawa Kiyoshi
Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Front Oncol. 2021 Aug 19;11:714527. doi: 10.3389/fonc.2021.714527. eCollection 2021.
Radical 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.
Tumor 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.
Using 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.
This novel method may enable rapid and real-time visualization of pancreatic cancer through the enzymatic activities of cancer tissues.
根治性切除术是胰腺癌唯一的治愈性治疗方法，胰腺癌是一种危及生命的疾病。然而，在手术前和手术过程中准确识别肿瘤范围往往并不容易。在此，我们描述了一种使用肿瘤特异性酶激活荧光探针检测胰腺肿瘤的新方法。
从切除标本中选取肿瘤和非肿瘤裂解物或小标本，以作为区分癌组织和非癌组织的最合适荧光探针。将选定的探针喷洒在癌组织切除标本的切面上以获取荧光图像。接下来，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来计算肿瘤与背景比值（TBR）。最后，我们寻找一种能最佳激活选定探针的肿瘤特异性酶。
使用包含309种独特荧光探针的文库，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张与肿瘤的病理结果相近，其TBR最高。最后，二肽基肽酶IV（DPP-IV）或一种类似DPP-IV的酶被确定为靶酶。
这种新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。
