Peptide-based PET imaging agent of tumor TIGIT expression

EJNMMI Research

Original Research

Rong Guo¹  Yu Gao¹  Ziyang Zhu¹  Rui An¹  Dinghu Weng²  Xiuman Zhou³ 

[1] Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 430000, Wuhan, Hubei, China;Hubei Province Key Laboratory of Molecular Imaging, 430000, Wuhan, Hubei, China;Department of Radiology, Zhongnan Hospital of Wuhan University, 430071, Wuhan, Hubei, China;School of Pharmaceutical Sciences (Shenzhen), SunYat-Sen University, 518107, Shenzhen, Guangdong, China;

关键词: Immune checkpoint;    TIGIT;    Ga;    Peptide;    Radiotracer;    Immunotherapy;   

DOI  :  10.1186/s13550-023-00982-7

 received in 2022-07-03, accepted in 2023-04-07,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundAccumulating studies have demonstrated that elevated TIGIT expression in tumor microenvironment correlates with better therapeutic response to TIGIT-based immunotherapy in pre-clinical studies. Therefore, a non-invasive method to detect tumor TIGIT expression is crucial to predict the therapeutic effect.MethodsIn this study, a peptide-based PET imaging agent, 68Ga-DOTA-DTBP-3, was developed to non-invasively detect TIGIT expression by micro-PET in tumor-bearing BALB/c mice. DTBP-3, a D-peptide comprising of 12 amino acids, was radiolabeled with 68Ga through a DOTA chelator. In vitro studies were performed to evaluate the affinity of 68Ga-DOTA-DTBP-3 to TIGIT and its stability in fetal bovine serum. In vivo studies were assessed by micro-PET, biodistribution, and immunohistochemistry on tumor-bearing BALB/c mice.ResultsThe in vitro studies showed the equilibrium dissociation constant of 68Ga-DOTA-DTBP-3 for TIGIT was 84.21 nM and its radiochemistry purity was 89.24 ± 1.82% in FBS at 4 h in room temperature. The results of micro-PET, biodistribution and immunohistochemistry studies indicated that 68Ga-DOTA-DTBP-3 could be specifically targeted in 4T1 tumor-bearing mice, with a highest uptake at 0.5 h.Conclusion68Ga-DOTA-DTBP-3 holds potential for non-invasively detect tumor TIGIT expression and for timely assessment of the therapeutic effect of immune checkpoint blockade.

【 授权许可】

CC BY   
© The Author(s) 2023

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