Citation: Qi Luo, Yunwei Zhang, Zihua Wang, Yining Sun, Linqing Shi, Yue Yu, Jiyun Shi, Zhiyuan Hu, Fan Wang. A novel peptide-based probe ^99mTc-PEG₆-RD-PDP2 for the molecular imaging of tumor PD-L2 expression[J]. Chinese Chemical Letters, ;2022, 33(7): 3497-3501. doi: 10.1016/j.cclet.2022.02.068 shu

A novel peptide-based probe ^99mTc-PEG₆-RD-PDP2 for the molecular imaging of tumor PD-L2 expression

Qi Luo ^{a, 1} ,
Yunwei Zhang ^{b, 1} ,
Zihua Wang ^{c, 1} ,
Yining Sun ^d ,
Linqing Shi ^b ,
Yue Yu ^d ,
Jiyun Shi ^{d, *,} ,
Zhiyuan Hu ^{c, e, *,} ,
Fan Wang ^{a, b, d, *,}

a.
Guangzhou Laboratory, Guangzhou 510005, China
b.
Medical Isotopes Research Center and Department of Radiation Medicine, State Key Laboratory of Natural and Biomimetic Drugs, School of Basic Medical Sciences, Peking University, Beijing 100191, China
c.
Fujian Provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350122, China
d.
Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
e.
CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, China

shijiyun@ibp.ac.cn

huzy@nanoctr.cn

wangfan@bjmu.edu.cn

Received Date: 23 December 2021
Revised Date: 25 February 2022
Accepted Date: 25 February 2022
Available Online: 1 March 2022

Figures(5)

Tumor-related PD-L2 expression is associated with the clinical efficacy of PD-1/PD-L1 blockade therapy. PD-L2-specific imaging can help selecting patients for appropriate immunotherapy. In this study, a PD-L2-targeting peptide (PDP2) was screened by the one-bead one-compound combinatorial library approach. Using the retro-inverso D-peptide of PDP2 (RD-PDP2) and PEGylation strategies, we developed a novel Tc-99m-labeled PD-L2-targeting peptide as a SPECT tracer (^99mTc-PEG₆-RD-PDP2) for imaging of tumor PD-L2 expression. The radiolabeling yield of ^99mTc-PEG₆-RD-PDP2 was greater than 95% by the standard HYNIC/tricine/TPPTS labeling procedure. ^99mTc-PEG₆-RD-PDP2 displayed high PD-L2-binding specificity both in vitro and in vivo. SPECT/CT imaging with ^99mTc-PEG₆-RD-PDP2 showed that the A549-PD-L2 tumors were clearly visualized, whereas the signals in PD-L2-negative A549 tumors were much lower. In vivo blocking study suggested that the tumor uptake of ^99mTc-PEG₆-RD-PDP2 was PD-L2 specifically mediated. ^99mTc-PEG₆-RD-PDP2 is a promising SPECT probe for the non-invasive imaging of tumor PD-L2 expression and has a great potential in guiding the anti-PD-1 or anti-PD-L1 immunotherapy of cancer.
- PD-L2,
- Peptide probe,
- SPECT imaging,
- Immunotherapy
1. [1]
  R.S. Herbst, J.C. Soria, M. Kowanetz, et al., Nature 515 (2014) 563-567. doi: 10.1038/nature14011
2. [2]
  S.M. Ansell, A.M. Lesokhin, I. Borrello, et al., N. Engl. J. Med. 372 (2015) 311-319. doi: 10.1056/NEJMoa1411087
3. [3]
  A. Haslam, V. Prasad, J.A.M.A. Netw. Open 2 (2019) e192535-e192543. doi: 10.1001/jamanetworkopen.2019.2535
4. [4]
  N. Wan, T.T. Zhang, S.H. Hua, et al., Cancer Med. 9 (2020) 1683-1693. doi: 10.1002/cam4.2793
5. [5]
  Q. Chen, T. Li, W. Yue, Onco Targets ther. 11 (2018) 4673. doi: 10.2147/OTT.S168313
6. [6]
  M. Yi, D. Jiao, H. Xu, et al., Mol. cancer 17 (2018) 1-14.
7. [7]
  A.V. Balar, D. Castellano, P.H. O'Donnell, et al., Lancet Oncol. 18 (2017) 1483-1492. doi: 10.1016/S1470-2045(17)30616-2
8. [8]
  E.G. Leprieur, C. Dumenil, C. Julie, et al., Eur. J. Cancer 78 (2017) 16-23. doi: 10.1016/j.ejca.2016.12.041
9. [9]
  L.Q. Chow, R. Haddad, S. Gupta, et al., J. Clin. Oncol. 34 (2016) 3838-3845. doi: 10.1200/JCO.2016.68.1478
10. [10]
  R.J. Motzer, B. Escudier, D.F. McDermott, et al., N. Engl. J. Med. 373 (2015) 1803-1813. doi: 10.1056/NEJMoa1510665
11. [11]
  D.P. Carbone, M. Reck, L. Paz-Ares, et al., N. Engl. J. Med. 376 (2017) 2415-2426. doi: 10.1056/NEJMoa1613493
12. [12]
  P. Sharma, M.K. Callahan, P. Bono, et al., Lancet Oncol. 17 (2016) 1590-1598. doi: 10.1016/S1470-2045(16)30496-X
13. [13]
  H. Wang, H. Yao, C. Li, et al., Oncoimmunology 6 (2017) e1327494-e1327504. doi: 10.1080/2162402X.2017.1327494
14. [14]
  H. Yang, X. Zhou, L. Sun, Y. Mao, Front. Oncol. 9 (2019) 47-58. doi: 10.3389/fonc.2019.00047
15. [15]
  J. Liu, H. Li, L. Sun, Y. Yuan, C. Xing, Biomed. Res. Int. 2020 (2020) 2496582-2496592.
16. [16]
  Y. Yang, X. Wang, Y. Bai, et al., Urol. Oncol. 38 (2020) 603. e609-603. e615.
17. [17]
  Y.R. Miao, K.N. Thakkar, J. Qian, et al., Clin. Cancer Res. 27 (2021) 4435-4448. doi: 10.1158/1078-0432.ccr-20-0482
18. [18]
  P. Youngnak, Y. Kozono, H. Kozono, et al., Biochem. Biophys. Res. Commun. 307 (2003) 672-677. doi: 10.1016/S0006-291X(03)01257-9
19. [19]
  Y. Latchman, C.R. Wood, T. Chernova, et al., Nat. Immunol. 2 (2001) 261-268. doi: 10.1038/85330
20. [20]
  D.M. Pardoll, Nat. Rev. Cancer 12 (2012) 252-264. doi: 10.1038/nrc3239
21. [21]
  T. Tanegashima, Y. Togashi, K. Azuma, et al., Clin. Cancer Res. 25 (2019) 4808-4819. doi: 10.1158/1078-0432.ccr-18-3991
22. [22]
  J.H. Yearley, C. Gibson, N. Yu, et al., Clin. Cancer Res. 23 (2017) 3158-3167.
23. [23]
  S.C. Liang, Y.E. Latchman, J.E. Buhlmann, et al., Eur. J. Immunol. 33 (2003) 2706-2716. doi: 10.1002/eji.200324228
24. [24]
  K. Broos, Q. Lecocq, G. Raes, et al., Theranostics 8 (2018) 3559-3570. doi: 10.7150/thno.24762
25. [25]
  Z. Wang, W. Wang, X. Bu, et al., Anal. Chem. 87 (2015) 8367-8372. doi: 10.1021/acs.analchem.5b01588
26. [26]
  W. Wang, M. Li, Z. Wei, et al., Anal. Chem. 86 (2014) 3703-3707. doi: 10.1021/ac500465e
27. [27]
  L. Li, Y. Wu, Z. Wang, et al., J. Nucl. Med. 58 (2017) 821-826. doi: 10.2967/jnumed.116.183863
28. [28]
  M. Seia, E. Zisman, FASEB J. 11 (1997) 449-456. doi: 10.1096/fasebj.11.6.9194525
29. [29]
  R. Tugyi, K. Uray, D. Iván, et al., Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 413-418. doi: 10.1073/pnas.0407677102
30. [30]
  B. Jia, J. Shi, Z. Yang, et al., Bioconjug. Chem. 17 (2006) 1069-1076. doi: 10.1021/bc060055b
31. [31]
  Q. Luo, G. Yang, H. Gao, et al., Bioconjug. Chem. 31 (2020) 1510-1521. doi: 10.1021/acs.bioconjchem.0c00170
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沈阳化工大学材料科学与工程学院沈阳 110142

A novel peptide-based probe 99mTc-PEG6-RD-PDP2 for the molecular imaging of tumor PD-L2 expression

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通讯作者: 陈斌, bchen63@163.com

A novel peptide-based probe ^99mTc-PEG₆-RD-PDP2 for the molecular imaging of tumor PD-L2 expression