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Title: Novel dual-function near-infrared II fluorescence and PET probe for tumor delineation and image-guided surgery

Abstract

Accurate tumor identification is essential in cancer management. Incomplete excision of tumor tissue, however, negatively affects the prognosis of the patient. To accomplish radical excision of tumor tissue, radiotracers can be used that target tumor tissue and can be detected using a gamma probe during surgery. Intraoperative fluorescence imaging could allow accurate real-time tumor delineation. Herein, a novel dual-modal imaging platform using base-catalyzed double addition of thiols into a propiolamide scaffold has been developed, allowing for the highly efficient and selective assembly of various thiol units in a protecting-group-free manner. The first small-molecule based αvβ3-targeted NIR-II/PET probe 68Ga-SCH2 was concisely generated via this strategy and subsequently evaluated in mice bearing the U87MG xenograft. Excellent imaging properties such as good tumor uptake, high tumor contrast and specificity, tumor delineation and image-guided surgery were achieved in the small animal models. These attractive results of 68Ga-SCH2 allow it to be a promising αvβ3-targeted NIR-II/PET probe for clinical translation.

Authors:
 [1];  [1];  [1];  [2];  [2];  [1];  [1];  [3];  [3];  [4];  [4];  [5];  [5];  [1];  [2]; ORCiD logo [1]
+ Show Author Affiliations
  1. State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (MOE) and Hubei Province Engineering and Technology Research Center for Fluorinated Pharmaceuticals, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China
  2. Molecular Imaging Program at Stanford (MIPS), Bio-X Program, Department of Radiology, Stanford University, USA
  3. Medical College, Tibet University, Lasa, China
  4. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Center for Experimental Basic Medical Education, Wuhan University, Wuhan 430071, China
  5. Department of Nuclear Medicine, The Second Hospital of Zhejiang University School of Medicine, Hangzhou, China
Publication Date:
Research Org.:
Stanford Univ., CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER)
OSTI Identifier:
1417921
Alternate Identifier(s):
OSTI ID: 1506079
Grant/Contract Number:  
SC0008397
Resource Type:
Published Article
Journal Name:
Chemical Science
Additional Journal Information:
Journal Name: Chemical Science Journal Volume: 9 Journal Issue: 8; Journal ID: ISSN 2041-6520
Publisher:
Royal Society of Chemistry (RSC)
Country of Publication:
United Kingdom
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE

Citation Formats

Sun, Yao, Zeng, Xiaodong, Xiao, Yuling, Liu, Changhao, Zhu, Hua, Zhou, Hui, Chen, Ziyang, Xu, Fuchun, Wang, Jule, Zhu, Mengyue, Wu, Junzhu, Tian, Mei, Zhang, Hong, Deng, Zixin, Cheng, Zhen, and Hong, Xuechuan. Novel dual-function near-infrared II fluorescence and PET probe for tumor delineation and image-guided surgery. United Kingdom: N. p., 2018. Web. doi:10.1039/C7SC04774F.
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Sun, Yao, Zeng, Xiaodong, Xiao, Yuling, Liu, Changhao, Zhu, Hua, Zhou, Hui, Chen, Ziyang, Xu, Fuchun, Wang, Jule, Zhu, Mengyue, Wu, Junzhu, Tian, Mei, Zhang, Hong, Deng, Zixin, Cheng, Zhen, & Hong, Xuechuan. Novel dual-function near-infrared II fluorescence and PET probe for tumor delineation and image-guided surgery. United Kingdom. https://doi.org/10.1039/C7SC04774F
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Sun, Yao, Zeng, Xiaodong, Xiao, Yuling, Liu, Changhao, Zhu, Hua, Zhou, Hui, Chen, Ziyang, Xu, Fuchun, Wang, Jule, Zhu, Mengyue, Wu, Junzhu, Tian, Mei, Zhang, Hong, Deng, Zixin, Cheng, Zhen, and Hong, Xuechuan. Mon . "Novel dual-function near-infrared II fluorescence and PET probe for tumor delineation and image-guided surgery". United Kingdom. https://doi.org/10.1039/C7SC04774F.
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@article{osti_1417921,
title = {Novel dual-function near-infrared II fluorescence and PET probe for tumor delineation and image-guided surgery},
author = {Sun, Yao and Zeng, Xiaodong and Xiao, Yuling and Liu, Changhao and Zhu, Hua and Zhou, Hui and Chen, Ziyang and Xu, Fuchun and Wang, Jule and Zhu, Mengyue and Wu, Junzhu and Tian, Mei and Zhang, Hong and Deng, Zixin and Cheng, Zhen and Hong, Xuechuan},
abstractNote = {Accurate tumor identification is essential in cancer management. Incomplete excision of tumor tissue, however, negatively affects the prognosis of the patient. To accomplish radical excision of tumor tissue, radiotracers can be used that target tumor tissue and can be detected using a gamma probe during surgery. Intraoperative fluorescence imaging could allow accurate real-time tumor delineation. Herein, a novel dual-modal imaging platform using base-catalyzed double addition of thiols into a propiolamide scaffold has been developed, allowing for the highly efficient and selective assembly of various thiol units in a protecting-group-free manner. The first small-molecule based αvβ3-targeted NIR-II/PET probe 68Ga-SCH2 was concisely generated via this strategy and subsequently evaluated in mice bearing the U87MG xenograft. Excellent imaging properties such as good tumor uptake, high tumor contrast and specificity, tumor delineation and image-guided surgery were achieved in the small animal models. These attractive results of 68Ga-SCH2 allow it to be a promising αvβ3-targeted NIR-II/PET probe for clinical translation.},
doi = {10.1039/C7SC04774F},
journal = {Chemical Science},
number = 8,
volume = 9,
place = {United Kingdom},
year = {Mon Jan 01 00:00:00 EST 2018},
month = {Mon Jan 01 00:00:00 EST 2018}
}
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Journal Article:
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Publisher's Version of Record
https://doi.org/10.1039/C7SC04774F
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Cited by: 135 works
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Figures / Tables:

Fig. 1 Fig. 1: A new strategy for the construction of NIR-II dual-modal imaging probes. (a) The previous photo-catalyzed thiol-yne reaction; (b) the approach discussed in the present work.
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