Volume 14 Issue 4
Jul.  2023
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WEN Xuejun, ZHOU Wuhao, GUO Zhide, ZHANG Xianzhong. Integrin αvβ3 Targeted Radiopharmaceutical 99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(4): 766-773. doi: 10.12290/xhyxzz.2023-0155
Citation: WEN Xuejun, ZHOU Wuhao, GUO Zhide, ZHANG Xianzhong. Integrin αvβ3 Targeted Radiopharmaceutical 99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy[J]. Medical Journal of Peking Union Medical College Hospital, 2023, 14(4): 766-773. doi: 10.12290/xhyxzz.2023-0155

Integrin αvβ3 Targeted Radiopharmaceutical 99mTc-RGD Combined with Anti-PD-L1 mAb to Enhance the Anti-tumor Effect in Tumor Immunotherapy

doi: 10.12290/xhyxzz.2023-0155
Funds:

National Natural Science Foundation of China 81901805

National Natural Science Foundation of China 21976150

National Natural Science Foundation of China 21906135

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  • Corresponding author: GUO Zhide, E-mail: gzd666888@xmu.edu.cn; ZHANG Xianzhong, E-mail: zhangxzh@hotmail.com
  • Received Date: 2023-03-28
  • Accepted Date: 2023-07-03
  • Available Online: 2023-07-26
  • Publish Date: 2023-07-30
  •   Objective  To investigate the effect of 99mTc-labeled RGD peptide (99mTc-RGD) on regulating the tumor immune microenvironment and enhancing the anti-tumor effect of immunotherapy when combined with anti-programmed death-ligand 1 (PD-L1) antibody.  Methods  The expression of PD-L1 on tumor cells was detected by flow cytometry, and the distribution of 99mTc-RGD in MC38 tumor mice was evaluated using single photon emission computed tomography(SPECT) imaging. The combination therapy was performed to monitor the anti-tumor effect.  Results  The expression of PD-L1 on CT26, MC38, 4T1 and B16F10 tumor cells was upregulated after being induced by 99mTc-RGD, and there was a statistical significance between 99mTc-RGD treated and untreated groups. Subsequently, SPECT imaging was performed by injecting 99mTc-RGD into MC38 tumor-bearing mice, and significant tumor uptake was observed. Based on this, the combination of 99mTc-RGD and anti-PD-L1 antibody in MC38 tumor mice was studied, and the results showed that different doses and time windows had significant effects on the efficacy of the combination therapy. The combination of 18.5 MBq or 37 MBq 99mTc-RGD with an anti-PD-L1 antibody led to the best therapeutic effect at 4 h intervals.  Conclusions  99mTc-RGD could induce the upregulation of tumor PD-L1 expression, and when combined with an anti-PD-L1 antibody, it could enhance the anti-tumor effect.
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