In Vivo Nitroreductase Imaging via Fluorescence and Chemical Shift Dependent 19F NMR
Dr. Shizhen Chen
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
These authors contributed equally to this work.
Search for more papers by this authorLong Xiao
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Yu Li
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorMaosong Qiu
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Yaping Yuan
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Rui Zhou
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Conggang Li
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Lei Zhang
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Zhong-Xing Jiang
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Maili Liu
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Xin Zhou
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Shizhen Chen
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
These authors contributed equally to this work.
Search for more papers by this authorLong Xiao
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
These authors contributed equally to this work.
Search for more papers by this authorDr. Yu Li
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorMaosong Qiu
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Yaping Yuan
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Rui Zhou
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Conggang Li
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorDr. Lei Zhang
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Zhong-Xing Jiang
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorProf. Dr. Maili Liu
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorCorresponding Author
Prof. Dr. Xin Zhou
State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences—Wuhan National Laboratory for Optoelectronics, Wuhan, 430071 (P. R. China
University of Chinese Academy of Sciences, Beijing, 100049 China
Search for more papers by this authorAbstract
Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual-mode NIR fluorescence and 19F MRI agent, FCy7-NO2, is proposed for imaging tumor hypoxia. We show that FCy7-NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19F MR chemical shift-sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7-NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue-depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment.
Conflict of interest
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
Filename | Description |
---|---|
ange202213495-sup-0001-misc_information.pdf2.2 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1H. Sung, J. Ferlay, R. L. Siegel, M. Laversanne, I. Soerjomataram, A. Jemal, F. Bray, Ca-Cancer J. Clin. 2021, 71, 209–249.
- 2
- 2aH. J. de Koning, C. M. van der Aalst, P. A. de Jong, E. T. Scholten, K. Nackaerts, M. A. Heuvelmans, J.-W. J. Lammers, C. Weenink, U. Yousaf-Khan, N. Horeweg, S. van ’t Westeinde, M. Prokop, W. P. Mali, F. A. A. Mohamed Hoesein, P. M. A. van Ooijen, J. G. J. V. Aerts, M. A. den Bakker, E. Thunnissen, J. Verschakelen, R. Vliegenthart, J. E. Walter, K. ten Haaf, H. J. M. Groen, M. Oudkerk, N. Engl. J. Med. 2020, 382, 503–513;
- 2bD. R. Aberle, A. M. Adams, C. D. Berg, W. C. Black, J. D. Clapp, R. M. Fagerstrom, I. F. Gareen, C. Gatsonis, P. M. Marcus, J. D. Sicks, N. Engl. J. Med. 2011, 365, 395–409.
- 3
- 3aG. B. Frisoni, N. C. Fox, C. R. Jack, P. Scheltens, P. M. Thompson, Nat. Rev. Neurol. 2010, 6, 67–77;
- 3bJ. P. B. O′Connor, A. Jackson, G. J. M. Parker, C. Roberts, G. C. Jayson, Nat. Rev. Clin. Oncol. 2012, 9, 167–177;
- 3cJ. Lu, J. Sun, F. Li, J. Wang, J. Liu, D. Kim, C. Fan, T. Hyeon, D. Ling, J. Am. Chem. Soc. 2018, 140, 10071–10074;
- 3dL. Wang, Z. Wang, X. Li, Y. Zhang, M. Yin, J. Li, H. Song, J. Shi, D. Ling, L. Wang, N. Chen, C. Fan, Nano Res. 2018, 11, 2746–2755.
- 4A. S. Khan, R. L. Harvey, J. R. Birchall, R. K. Irwin, P. Nikolaou, G. Schrank, K. Emami, A. Dummer, M. J. Barlow, B. M. Goodson, E. Y. Chekmenev, Angew. Chem. Int. Ed. 2021, 60, 22126–22147; Angew. Chem. 2021, 133, 22298–22319.
- 5
- 5aR. Shusterman-Krush, N. D. Tirukoti, A. K. Bandela, L. Avram, H. Allouche-Arnon, X. Cai, B. C. Gibb, A. Bar-Shir, Angew. Chem. Int. Ed. 2021, 60, 15405–15411; Angew. Chem. 2021, 133, 15533–15539;
- 5bK. Akazawa, F. Sugihara, T. Nakamura, H. Matsushita, H. Mukai, R. Akimoto, M. Minoshima, S. Mizukami, K. Kikuchi, Angew. Chem. Int. Ed. 2018, 57, 16742–16747; Angew. Chem. 2018, 130, 16984–16989.
- 6
- 6aJ. M. Brown, W. R. Wilson, Nat. Rev. Cancer 2004, 4, 437–447;
- 6bW. R. Wilson, M. P. Hay, Nat. Rev. Cancer 2011, 11, 393–410.
- 7I. Dagogo-Jack, A. T. Shaw, Nat. Rev. Clin. Oncol. 2018, 15, 81–94.
- 8
- 8aY. Ye, Q. Hu, H. Chen, K. Liang, Y. Yuan, Y. Xiang, H. Ruan, Z. Zhang, A. Song, H. Zhang, L. Liu, L. Diao, Y. Lou, B. Zhou, L. Wang, S. Zhou, J. Gao, E. Jonasch, S. H. Lin, Y. Xia, C. Lin, L. Yang, G. B. Mills, H. Liang, L. Han, Nat. Metab. 2019, 1, 431–444;
- 8bC.-C. Huang, W.-T. Chia, M.-F. Chung, K.-J. Lin, C.-W. Hsiao, C. Jin, W.-H. Lim, C.-C. Chen, H.-W. Sung, J. Am. Chem. Soc. 2016, 138, 5222–5225;
- 8cS. Kuang, L. Sun, X. Zhang, X. Liao, T. W. Rees, L. Zeng, Y. Chen, X. Zhang, L. Ji, H. Chao, Angew. Chem. Int. Ed. 2020, 59, 20697–20703; Angew. Chem. 2020, 132, 20878–20884.
- 9
- 9aC. Huang, W. Tan, J. Zheng, C. Zhu, J. Huo, R. Yang, ACS Appl. Mater. Interfaces 2019, 11, 25740–25749;
- 9bS. Danson, T. H. Ward, J. Butler, M. Ranson, Cancer Treat. Rev. 2004, 30, 437–449;
- 9cY. Zhang, W. Zhao, Y. Chen, H. Yuan, H. Fang, S. Yao, C. Zhang, H. Xu, N. Li, Z. Liu, Z. Guo, Q. Zhao, Y. Liang, W. He, Nat. Commun. 2021, 12, 2772;
- 9dS. He, J. Li, Y. Lyu, J. Huang, K. Pu, J. Am. Chem. Soc. 2020, 142, 7075–7082;
- 9eW.-C. Geng, S. Jia, Z. Zheng, Z. Li, D. Ding, D.-S. Guo, Angew. Chem. Int. Ed. 2019, 58, 2377–2381; Angew. Chem. 2019, 131, 2399–2403;
- 9fL. Sun, Y. Gao, Y. Xu, J. Chao, H. Liu, L. Wang, D. Li, C. Fan, J. Am. Chem. Soc. 2017, 139, 17525–17532;
- 9gF. Wang, Y. Zhu, L. Zhou, L. Pan, Z. Cui, Q. Fei, S. Luo, D. Pan, Q. Huang, R. Wang, C. Zhao, H. Tian, C. Fan, Angew. Chem. Int. Ed. 2015, 54, 7349–7353; Angew. Chem. 2015, 127, 7457–7461;
- 9hJ. Huang, X. Chen, Y. Jiang, C. Zhang, S. He, H. Wang, K. Pu, Nat. Mater. 2022, 21, 598–607.
- 10
- 10aS. Curado, D. Y. R. Stainier, R. M. Anderson, Nat. Protoc. 2008, 3, 948–954;
- 10bY. Liu, L. Teng, L. Chen, H. Ma, H.-W. Liu, X.-B. Zhang, Chem. Sci. 2018, 9, 5347–5353;
- 10cH. J. Knox, J. Hedhli, T. W. Kim, K. Khalili, L. W. Dobrucki, J. Chan, Nat. Commun. 2017, 8, 1794;
- 10dB. Brennecke, Q. Wang, Q. Zhang, H.-Y. Hu, M. Nazaré, Angew. Chem. Int. Ed. 2020, 59, 8512–8516; Angew. Chem. 2020, 132, 8590–8594.
- 11Z. Thiel, P. Rivera-Fuentes, Angew. Chem. Int. Ed. 2019, 58, 11474–11478; Angew. Chem. 2019, 131, 11597–11602.
- 12Y. Li, Y. Sun, J. Li, Q. Su, W. Yuan, Y. Dai, C. Han, Q. Wang, W. Feng, F. Li, J. Am. Chem. Soc. 2015, 137, 6407–6416.
- 13Y. Jiao, L. Zhang, X. Gao, W. Si, C. Duan, Angew. Chem. Int. Ed. 2020, 59, 6021–6027; Angew. Chem. 2020, 132, 6077–6083.
- 14A. Louie, Chem. Rev. 2010, 110, 3146–3195.
- 15R. Yan, Y. Hu, F. Liu, S. Wei, D. Fang, A. J. Shuhendler, H. Liu, H.-Y. Chen, D. Ye, J. Am. Chem. Soc. 2019, 141, 10331–10341.
- 16J. H. Jang, S. Bhuniya, J. Kang, A. Yeom, K. S. Hong, J. S. Kim, Org. Lett. 2013, 15, 4702–4705.
- 17
- 17aJ. Ouyang, L. Sun, Z. Zeng, C. Zeng, F. Zeng, S. Wu, Angew. Chem. Int. Ed. 2020, 59, 10111–10121; Angew. Chem. 2020, 132, 10197–10207;
- 17bA. Chevalier, Y. Zhang, O. M. Khdour, J. B. Kaye, S. M. Hecht, J. Am. Chem. Soc. 2016, 138, 12009–12012.
- 18D. Cui, J. Huang, X. Zhen, J. Li, Y. Jiang, K. Pu, Angew. Chem. Int. Ed. 2019, 58, 5920–5924; Angew. Chem. 2019, 131, 5981–5985.
- 19A. Dougherty Dennis, Science 1996, 271, 163–168.
- 20
- 20aJ. Yin, Y. Kwon, D. Kim, D. Lee, G. Kim, Y. Hu, J.-H. Ryu, J. Yoon, Nat. Protoc. 2015, 10, 1742–1754;
- 20bZ. Zeng, S. S. Liew, X. Wei, K. Pu, Angew. Chem. Int. Ed. 2021, 60, 26454–26475; Angew. Chem. 2021, 133, 26658–26679.
- 21R. B. Altman, D. S. Terry, Z. Zhou, Q. Zheng, P. Geggier, R. A. Kolster, Y. Zhao, J. A. Javitch, J. D. Warren, S. C. Blanchard, Nat. Methods 2012, 9, 68–71.
- 22
- 22aW. Wang, J. J. Han, L.-Q. Wang, L.-S. Li, W. J. Shaw, A. D. Q. Li, Nano Lett. 2003, 3, 455–458;
- 22bM. O. Sinnokrot, C. D. Sherrill, J. Am. Chem. Soc. 2004, 126, 7690–7697.
- 23
- 23aH. Abdullah, N. S. Gultom, H. Shuwanto, W. L. Kebede, D.-H. Kuo, ACS Appl. Mater. Interfaces 2020, 12, 43761–43770;
- 23bW. Eck, V. Stadler, W. Geyer, M. Zharnikov, A. Gölzhäuser, M. Grunze, Adv. Mater. 2000, 12, 805–808;
- 23cB. Shi, N. Ren, L. Gu, G. Xu, R. Wang, T. Zhu, Y. Zhu, C. Fan, C. Zhao, H. Tian, Angew. Chem. Int. Ed. 2019, 58, 16826–16830; Angew. Chem. 2019, 131, 16982–16986.
- 24R. Wang, J. Chen, J. Gao, J.-A. Chen, G. Xu, T. Zhu, X. Gu, Z. Guo, W.-H. Zhu, C. Zhao, Chem. Sci. 2019, 10, 7222–7227.
- 25M. Zhang, H. Li, H. Li, X. Zhao, Q. Zhou, Q. Rao, Y. Han, Y. Lan, H. Deng, X. Sun, X. Lou, C. Ye, X. Zhou, Magn. Reson. Med. 2020, 84, 569–578.
This is the
German version
of Angewandte Chemie.
Note for articles published since 1962:
Do not cite this version alone.
Take me to the International Edition version with citable page numbers, DOI, and citation export.
We apologize for the inconvenience.