Chu Tang1,2, Yang Du2,3,4, Qian Liang2, Zhen Cheng5, Jie Tian6,7,8,9,10. 1. Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, 710126, Shaanxi, China. 2. CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. 3. Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China. 4. University of Chinese Academy of Sciences, Beijing, 100080, China. 5. Molecular Imaging Program at Stanford (MIPS), Department of Radiology, and Bio-X Program, Canary Center at Stanford for Cancer Early Detection, Stanford University, Stanford, CA, 94305-5344, USA. zcheng@stanford.edu. 6. Engineering Research Center of Molecular and Neuro Imaging, Ministry of Education, School of Life Science and Technology, Xidian University, Xi'an, 710126, Shaanxi, China. jie.tian@ia.ac.cn. 7. CAS Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. jie.tian@ia.ac.cn. 8. Beijing Key Laboratory of Molecular Imaging, Beijing, 100190, China. jie.tian@ia.ac.cn. 9. University of Chinese Academy of Sciences, Beijing, 100080, China. jie.tian@ia.ac.cn. 10. Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, 100191, China. jie.tian@ia.ac.cn.
Abstract
PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer worldwide, and complete surgical resection of diseased tissue is a reliable strategy to cure cancer. Fluorescence image-guided surgery is a promising tool for surgeons to identify and remove malignant lesions. While non-targeted fluorescent dyes have been used for HCC diagnosis and resection, insufficient specificity and false positive uptake from inflammatory tissue result in a high recurrence rate or excessive excision of healthy liver tissue. To circumvent these problems, we focused on developing novel tumor-specific targeting probe to selectively illuminate cancer region during surgery. Given overexpression of histone deacetylases (HDACs) in HCC and many other cancers, HDAC-targeted imaging has been emerged as a promising tool for tumor detection. PROCEDURES: Recently, high expression of HDACs, in particular HDAC6, has been observed in tumor samples of HCC patient, and a few HDAC inhibitors, including FDA-approved suberoylanilide hydroxamic acid (SAHA), display potent antitumor effect on HCC. Correspondingly, in this study, we utilized a small molecule SAHA with the high HDAC-binding affinity as the HCC-specific targeting ligand to develop HDAC-targeted fluorescence probe for HCC detection and fluorescence image-guided resection. RESULTS: In in vitro imaging, SAHA was labelled with fluorescein isothiocyanate (FITC) to evaluate targeting property, and the imaging results demonstrated that FITC-SAHA was specific uptake by HCC Bel-7402 cells. In in vivo imaging, near infrared fluorescence dye IRDye800CW-labelled SAHA (NIR probe IRDye800CW-SAHA) showed rapid tumor accumulation with high tumor-to-background contrast on both the subcutaneous and orthotopic HCC mouse tumor models. Furthermore, the orthotopic HCC was successfully resected by the IRDye800CW-SAHA fluorescence image-guided surgery. Moreover, IRDye800CW-SAHA showed no toxicity toward healthy tissues. CONCLUSIONS: Our results indicate that IRDye800CW-SAHA is a clinical translatable probe for HCC detection and resection.
PURPOSE:Hepatocellular carcinoma (HCC) is a common cancer worldwide, and complete surgical resection of diseased tissue is a reliable strategy to cure cancer. Fluorescence image-guided surgery is a promising tool for surgeons to identify and remove malignant lesions. While non-targeted fluorescent dyes have been used for HCC diagnosis and resection, insufficient specificity and false positive uptake from inflammatory tissue result in a high recurrence rate or excessive excision of healthy liver tissue. To circumvent these problems, we focused on developing novel tumor-specific targeting probe to selectively illuminate cancer region during surgery. Given overexpression of histone deacetylases (HDACs) in HCC and many other cancers, HDAC-targeted imaging has been emerged as a promising tool for tumor detection. PROCEDURES: Recently, high expression of HDACs, in particular HDAC6, has been observed in tumor samples of HCC patient, and a few HDAC inhibitors, including FDA-approved suberoylanilide hydroxamic acid (SAHA), display potent antitumor effect on HCC. Correspondingly, in this study, we utilized a small molecule SAHA with the high HDAC-binding affinity as the HCC-specific targeting ligand to develop HDAC-targeted fluorescence probe for HCC detection and fluorescence image-guided resection. RESULTS: In in vitro imaging, SAHA was labelled with fluorescein isothiocyanate (FITC) to evaluate targeting property, and the imaging results demonstrated that FITC-SAHA was specific uptake by HCC Bel-7402 cells. In in vivo imaging, near infrared fluorescence dye IRDye800CW-labelled SAHA (NIR probe IRDye800CW-SAHA) showed rapid tumor accumulation with high tumor-to-background contrast on both the subcutaneous and orthotopic HCC mousetumor models. Furthermore, the orthotopic HCC was successfully resected by the IRDye800CW-SAHA fluorescence image-guided surgery. Moreover, IRDye800CW-SAHA showed no toxicity toward healthy tissues. CONCLUSIONS: Our results indicate that IRDye800CW-SAHA is a clinical translatable probe for HCC detection and resection.
Authors: Roberto Jose Diaz; Roberto Rey Dios; Eyas M Hattab; Kelly Burrell; Patricia Rakopoulos; Nesrin Sabha; Cynthia Hawkins; Gelareh Zadeh; James T Rutka; Aaron A Cohen-Gadol Journal: J Neurosurg Date: 2015-04-03 Impact factor: 5.115
Authors: Kiranya E Tipirneni; Jason M Warram; Lindsay S Moore; Andrew C Prince; Esther de Boer; Aditi H Jani; Irene L Wapnir; Joseph C Liao; Michael Bouvet; Nicole K Behnke; Mary T Hawn; George A Poultsides; Alexander L Vahrmeijer; William R Carroll; Kurt R Zinn; Eben Rosenthal Journal: Ann Surg Date: 2017-07 Impact factor: 12.969
Authors: W Stummer; S Stocker; S Wagner; H Stepp; C Fritsch; C Goetz; A E Goetz; R Kiefmann; H J Reulen Journal: Neurosurgery Date: 1998-03 Impact factor: 4.654
Authors: Charlotte E S Hoogstins; Quirijn R J G Tummers; Katja N Gaarenstroom; Cor D de Kroon; J Baptist M Z Trimbos; Tjalling Bosse; Vincent T H B M Smit; Jaap Vuyk; Cornelis J H van de Velde; Adam F Cohen; Philip S Low; Jacobus Burggraaf; Alexander L Vahrmeijer Journal: Clin Cancer Res Date: 2016-06-15 Impact factor: 12.531
Authors: Sravanth K Hindupur; Marco Colombi; Stephen R Fuhs; Matthias S Matter; Yakir Guri; Kevin Adam; Marion Cornu; Salvatore Piscuoglio; Charlotte K Y Ng; Charles Betz; Dritan Liko; Luca Quagliata; Suzette Moes; Paul Jenoe; Luigi M Terracciano; Markus H Heim; Tony Hunter; Michael N Hall Journal: Nature Date: 2018-03-21 Impact factor: 49.962
Authors: Lindsay Brammen; Martin B Niederle; Philipp Riss; Christian Scheuba; Andreas Selberherr; Georgios Karanikas; Gerd Bodner; Oskar Koperek; Bruno Niederle Journal: Ann Surg Oncol Date: 2018-10-10 Impact factor: 5.344
Authors: Mohammad Faysal Al Mazid; Seung Bin Park; Subba Rao Cheekatla; Dhiraj P Murale; Kyung Ho Shin; Jun-Seok Lee Journal: Int J Mol Sci Date: 2022-05-25 Impact factor: 6.208
Authors: Friederike Reeßing; Mafalda Bispo; Marina López-Álvarez; Marleen van Oosten; Ben L Feringa; Jan Maarten van Dijl; Wiktor Szymański Journal: ACS Omega Date: 2020-08-26