Rapid imaging of thymoma and thymic carcinoma with a fluorogenic probe targeting γ-glutamyltranspeptidase

利用针对 γ-谷氨酰转肽酶的荧光探针对胸腺瘤和胸腺癌进行快速成像

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作者:Daisuke Yoshida, Mako Kamiya, Shun Kawashima, Takafusa Yoshioka, Haruaki Hino, Atsuki Abe, Kyohhei Fujita, Ryosuke Kojima, Aya Shinozaki-Ushiku, Yasuteru Urano, Jun Nakajima

Abstract

In recent years, thoracoscopic and robotic surgical procedures have increasingly replaced median sternotomy for thymoma and thymic carcinoma. In cases of partial thymectomy, the prognosis is greatly improved by ensuring a sufficient margin from the tumor, and therefore intraoperative fluorescent imaging of the tumor is especially valuable in thoracoscopic and robotic surgery, where tactile information is not available. γ-Glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been applied for fluorescence imaging of some types of tumors in the resected tissues, and here we aimed to examine its validity for the imaging of thymoma and thymic carcinoma. 22 patients with thymoma or thymic carcinoma who underwent surgery between February 2013 and January 2021 were included in the study. Ex vivo imaging of specimens was performed, and the sensitivity and specificity of gGlu-HMRG were 77.3% and 100%, respectively. Immunohistochemistry (IHC) staining was performed to confirm expression of gGlu-HMRG's target enzyme, γ-glutamyltranspeptidase (GGT). IHC revealed high GGT expression in thymoma and thymic carcinoma in contrast to absent or low expression in normal thymic parenchyma and fat tissue. These results suggest the utility of gGlu-HMRG as a fluorescence probe for intraoperative visualization of thymomas and thymic carcinomas.

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